Stage II T Lymphoblastic Leukemia/LymphomaPhase 2/3NCT07072585
Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL)
A Phase 2/3 study testing Biopsy Procedure, Biospecimen Collection and Bone Marrow Aspiration in people with Stage II T Lymphoblastic Leukemia/Lymphoma and Stage III T Lymphoblastic Leukemia/Lymphoma, run by Children's Oncology Group.
Trial summary
This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Read more about this study
- Who is it for?
- Ages 365 days to 21 years
- Conditions the study is for
- Stage II T Lymphoblastic Leukemia/Lymphoma, Stage III T Lymphoblastic Leukemia/Lymphoma, Stage IV T Lymphoblastic Leukemia/Lymphoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Bone Marrow Aspiration
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,708 participants
- Where
- No sites listed yet
- Study dates
- 28 Aug 2026to 1 Sep 2035
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 365 days to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrolled on AALL2331.
- Patients must be > 365 days and < 21 years of age at the time of diagnosis.
- * Newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LL) stages II-IV.
- Note: A diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (CD19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow. If surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including TdT, CD34 or CD99 will be assessed for expression. Cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory.
- For T-LL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL. For tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LL defined by the submitting institution will be accepted.
Who cannot join
- Diagnosis of Down syndrome (trisomy 21).
- Patients with known Charcot-Marie-Tooth disease.
- * Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-LL or for any cancer diagnosis prior to the initiation of protocol therapy on AALL2331 with the exception of:
- Steroid pretreatment: Prednisone or methylprednisolone for ≤ 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for ≤ 336 hours (14 days) in the 28 days prior to initiation of protocol therapy does not affect eligibility.
- Intrathecal cytarabine; or
- Pretreatment with hydroxyurea; or
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- 600 cGy of chest irradiation, if medically necessary.
- Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during sedation to prevent or treat airway edema. Patients who receive a single dose of dexamethasone to prevent or treat airway edema in the 28 days preceding diagnosis are eligible for this study.
- * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
- Known severe persistent asthma anytime in the previous two years or uncontrolled asthma of any classification.
- Peripheral neurotoxicity: Pre-existing ≥ grade 2 sensory or motor peripheral neurotoxicity.
- Seizure disorder: Patients must not have an uncontrolled seizure disorder. Patients with a seizure history or a controlled seizure disorder are eligible. A controlled seizure disorder is defined as having stable or decreasing symptoms over the past 3 months without anti-epileptic medications or is on a stable or decreasing dose of anti-epileptic medication.
- * Patients who are previously known to be seropositive for HIV except for HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment on this trial.
- Patients with evidence of chronic hepatitis B (HBV) infection, except for patients who have an HBV viral load that is undetectable on suppressive therapy.
- Patients with a history of hepatitis C virus (HCV) infection, except for those patients who have been treated and cured, or patients who are currently on HCV treatment who have an undetectable HCV viral load.
- Patients with significant hepatic dysfunction defined as those with an alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) > 10x upper limit of normal (ULN) or direct bilirubin > 2x ULN unless the patient has known Gilbert's syndrome or has hepatic involvement from leukemic or lymphomatous infiltration.
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
About this study
Official title: A Phase 2/3 Randomized Trial Investigating Daratumumab on a Modified Augmented BFM (aBFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LL)
This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with daratumumab may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare the event-free survival (EFS) from the end of induction (EOI) in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Münster (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab.
II. To compare the EFS from the EOI in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab.
SECONDARY OBJECTIVES:
- To compare health-related quality of life (HRQoL) and therapy-related toxicity and tolerability between patients with T-ALL or T-LL randomized to a modified aBFM backbone or to a modified aBFM backbone with the addition of daratumumab.
II. To compare overall survival (OS) from date of randomization in patients with newly diagnosed T-ALL who are randomized to either receive a modified aBFM chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab.
III. To compare OS from date of randomization in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab.
EXPLORATORY OBJECTIVES:
- In patients with newly diagnosed T-LL, to determine if minimal residual disease (MRD) testing at EOI can predict EFS and/or OS.
II. In T-ALL patients, to describe changes in the immunophenotype (specifically CD38 surface expression on T-ALL/T-LL blasts) and for the development of anti-daratumumab antibodies over the course of treatment and correlate changes with clinical outcomes and demographic variables.
III. To explore the associations between family-reported social determinants of health and both clinical outcomes (including incidence of treatment-related toxicities, EFS, OS), and leukemia/lymphoma and host biology.
IV. To describe outcome differences (EFS and OS) in patients with T-LL who differ in degrees of positron emission tomography (PET)-imaging avid disease at the EOI.
- To explore potential imaging findings and biomarkers of significant/severe nelarabine-induced central nervous system toxicities by central review of magnetic resonance imaging (MRI) and to investigate possible clinical features in patients experiencing such toxicities.
VI. To bank peripheral blood specimens for future correlative studies in patients with T-LL.
VII. To compare EFS and OS from the EOI in patients with newly diagnosed T-ALL who are MRD positive (≥ 0.01%) at the EOI to those who are MRD negative at the EOI.
OUTLINE: This is a phase II study, followed by a phase III study. Patients are assigned to 1 of 2 groups.
GROUP I T-ALL:
INDUCTION: Patients receive cytarabine intrathecally (IT) once at the time of lumbar puncture, or day 1, daunorubicin intravenously (IV) over 1 - 15 minutes on days 1, 8, 15 and 22, dexamethasone orally (PO) or IV twice a day (BID) on days 1 - 28, vincristine IV on days 1, 8, 15 and 22, pegaspargase IV over 1 - 2 hours or intramuscularly (IM) once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and methotrexate IT on days 8 and 29 (patients with central nervous system [CNS]1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 8, 15, 22 and 29 (patients with CNS3). Induction treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
EOI: Patients are randomized to 1 of 2 arms.
ARM A:
CONSOLIDATION: Patients receive nelarabine IV over 60 minutes QD on days 1 - 5 and 36 - 40, cyclophosphamide IV over 30 - 60 minutes on days 8 and 43, cytarabine IV over 1 - 30 minutes or subcutaneously (SC) QD on days 8 - 11, 15 - 18, 43 - 46 and 50 - 53, mercaptopurine PO QD on days 8 - 21 and 43 - 56, methotrexate IT on days 15, 22, 50 and 57 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 15, 22, 50 and 57 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 22 and 57 or calaspargase pegol-mknl IV over 1 - 2 hours on days 22 and 57, and vincristine IV on days 22, 29, 57 and 64. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 77 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 1% following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 0.1% following interim maintenance proceed to delayed intensification.
DELAYED INTENSIFICATION:
PART 1: Patients receive dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and vincristine IV on days 1, 8 and 15. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive nelarabine IV over 60 minutes QD on days 29 - 33, cyclophosphamide IV over 30 - 60 minutes once on day 36, cytarabine IV over 1 - 30 minutes or SC QD on days 36 - 39 and 43 - 46, thioguanine PO QD on days 36 - 49, methotrexate IT on days 36 and 43 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 36 and 43 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 50 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 50, and vincristine IV on days 50 and 57. Delayed intensification part 2 treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
CYCLES 1 - 3: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 28 and 36 - 84, prednisone PO or IV BID on days 1 - 5 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5 and 57 - 61 or methylprednisolone IV BID on days 1 - 5 and 57 - 61, vincristine IV on days 1 and 57, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78, and nelarabine IV over 60 minutes QD on days 29 - 33. Cycles repeat every 84 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 4 +: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61, mercaptopurine PO QD on days 1 - 84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days until 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
ARM B:
CONSOLIDATION: Patients receive daratumumab IV on days 8, 15, 22, 29, 43, 50, 57 and 64, nelarabine IV over 60 minutes QD on days 1 - 5 and 36 - 41, cyclophosphamide IV over 30 - 60 minutes on days 8 and 43, cytarabine IV over 1 - 30 minutes or SC QD on days 8 - 11, 15 - 18, 43 - 46 and 50 - 53, mercaptopurine PO QD on days 8 - 21 and 43 - 56, methotrexate IT on days 15, 22, 50 and 57 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 15, 22, 50 and 57 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 23 and 58 or calaspargase pegol-mknl IV over 1 - 2 hours on days 23 and 58, and vincristine IV on days 22, 29, 57 and 64. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 77 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 1% following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive daratumumab IV on days 1, 21 and 41, methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 0.1% following interim maintenance proceed to delayed intensification.
DELAYED INTENSIFICATION:
PART 1: Patients receive daratumumab IV on days 1 and 15, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive nelarabine IV over 60 minutes QD on days 29 - 33, daratumumab IV on days 36 and 50, cyclophosphamide IV over 30 - 60 minutes once on day 36, cytarabine IV over 1 - 30 minutes or SC QD on days 36 - 39 and 43 - 46, thioguanine PO QD on days 36 - 49, methotrexate IT on days 36 and 43 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 36 and 43 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 51 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 51, and vincristine IV on days 50 and 57. Delayed intensification part 2 treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
CYCLES 1 - 3: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 28 and 36 - 84, prednisone PO or IV BID on days 1 - 5 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5 and 57 - 61 or methylprednisolone IV BID on days 1 - 5 and 57 - 61, vincristine IV on days 1 and 57, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78, and nelarabine IV over 60 minutes QD on days 29 - 33. Cycles repeat every 84 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 4 +: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61, mercaptopurine PO QD on days 1 - 84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days until 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo echocardiography (ECHO) during screening and bone marrow biopsy and aspiration as well as lumbar puncture throughout the study. Patients may undergo MRI, ultrasound and biopsy on study as well as may undergo blood sample collection throughout the study.
GROUP II T-LL:
INDUCTION: Patients receive bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 8 and 11, cytarabine IT once at the time of lumbar puncture, or day 1, daunorubicin IV over 1 - 15 minutes on days 1, 8, 15 and 22, prednisone PO or IV BID on days 1 - 28 or prednisolone PO or IV BID on days 1 - 28 or methylprednisolone IV BID on days 1 - 28, methotrexate IT on days 8 and 29 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 8, 15, 22 and 29 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and vincristine IV on days 1, 8, 15 and 22. Induction treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
EOI: Patients are randomized to 1 of 2 arms.
ARM C:
CONSOLIDATION: Patients receive cyclophosphamide IV over 30 - 60 minutes on days 1 and 29, cytarabine IV over 1 - 30 minutes or SC QD on days 1 - 4, 8 - 11, 29 - 32 and 36 - 39, mercaptopurine PO QD on days 1 - 14 and 29 - 42, methotrexate IT on days 1, 8, 15 and 22 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1, 8, 15 and 22 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 15 and 43 or calaspargase pegol-mknl IV over 1 - 2 hours on days 15 and 43, and vincristine IV on days 15, 22, 43 and 50. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION:
PART 1: Patients receive bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 15 and 18, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive cyclophosphamide IV over 30 - 60 minutes once on day 29, cytarabine IV over 1 - 30 minutes or SC QD on days 29 - 32 and 36 - 39, thioguanine PO QD on days 29 - 42, methotrexate IT on days 29 and 36 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 29 and 36 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 43 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 43, and vincristine IV on days 43 and 50. Delayed intensification part 2 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 84, prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or methylprednisolone IV BID on days 1 - 5, 29 - 33 and 57 - 61, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days for 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
ARM D:
CONSOLIDATION: Patients receive daratumumab IV on days 1, 8, 15, 22, 29, 36, 43 and 50, cyclophosphamide IV over 30 - 60 minutes on days 1 and 29, cytarabine IV over 1 - 30 minutes or SC QD on days 1 - 4, 8 - 11, 29 - 32 and 36 - 39, mercaptopurine PO QD on days 1 - 14 and 29 - 42, methotrexate IT on days 1, 8, 15 and 22 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1, 8, 15 and 22 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 16 and 44 or calaspargase pegol-mknl IV over 1 - 2 hours on days 16 and 44, and vincristine IV on days 15, 22, 43 and 50. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 63 days in the absence of disease progression or unacceptable toxicity. Patients with a CR following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive daratumumab IV on days 1, 21 and 41, methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION:
PART 1: Patients receive daratumumab IV on days 1 and 15, bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 15 and 18, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive daratumumab IV QD on days 29 and 43, cyclophosphamide IV over 30 - 60 minutes once on day 29, cytarabine IV over 1 - 30 minutes or SC QD on days 29 - 32 and 36 - 39, thioguanine PO QD on days 29 - 42, methotrexate IT QD on days 29 and 36 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT QD on days 29 and 36 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 44 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 44, and vincristine IV QD on days 43 and 50. Delayed intensification part 2 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 84, prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or methylprednisolone IV BID on days 1 - 5, 29 - 33 and 57 - 61, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days for 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo ECHO during screening and lumbar puncture as well as computed tomography (CT) or MRI, PET or PET-CT or bone scan throughout the study. Patients may undergo ultrasound and biopsy on study as well as may undergo blood sample collection and bone marrow biopsy and aspiration throughout the study.
After completion of study treatment, patients are followed up for 10 years.
- Conditions
- Stage II T Lymphoblastic Leukemia/Lymphoma, Stage III T Lymphoblastic Leukemia/Lymphoma, Stage IV T Lymphoblastic Leukemia/Lymphoma, T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Bone Scan
- Medical subject headings
- Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow biopsy
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, Boruzu, LDP 341, LDP-341
Given IV or SC
Calaspargase PegolDrug
Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IT or IV or SC
DaratumumabBiological
Also called Daratumumab Biosimilar HLX15, Daratumumab-fihj, Darzalex, HLX15
Given IV
Daunorubicin HydrochlorideDrug
Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Under lumbar puncture
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Mercaptopurine Oral SuspensionDrug
Also called 6-MP Oral Suspension, Purixan, Xaluprine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT or IV or PO
Also called Adlone, Caberdelta M, DepMedalone, Depo Moderin
Given IV
NelarabineDrug
Also called 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78
Given IV
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase
Given IV or IM
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET or PET-CT
PrednisoloneDrug
Also called (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione, .delta.1-Hydrocortisone, Adnisolone, Aprednislon
Given PO or IV
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO or IV
Questionnaire AdministrationOther
Ancillary studies
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo radiation therapy
Therapeutic HydrocortisoneDrug
Also called Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort
Given IT
ThioguanineDrug
Also called 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol
Given PO
Ultrasound ImagingProcedure or surgery
Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography
Undergo ultrasound
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Group I, Arm A (T-ALL, no daratumumab) | Active comparator | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate |
| Group I, Arm B (T-ALL, daratumumab) | Experimental | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Biological: Daratumumab; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate |
| Group II, Arm C (T-LL, no daratumumab) | Active comparator | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Drug: Bortezomib; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate |
| Group II, Arm D (T-LL, daratumumab) | Experimental | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Drug: Bortezomib; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Biological: Daratumumab; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL)
Will compare EFS in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Munich (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls). A phase 2/3 design will be used.
Measured: From date of randomization (randomization conducted at the end of induction [EOI]) to date of first event (consolidation failure, interim maintenance failure, relapse, secondary malignant neoplasm [SMN], death from any cause), assessed up to 4 years
EFS in patients with newly diagnosed T-cell lymphoblastic lymphoma (T-LL)
Will compare EFS in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls).
Measured: From date of randomization (randomization conducted at the EOI) to date of first event (consolidation failure, relapse, progressive disease, SMN, death from any cause), assessed up to 4 years
Secondary outcomes (4)
Health-related quality of life (HRQoL)
Will compare HRQoL between patients with T-ALL or T-LL randomized to a modified aBFM backbone or to a modified aBFM backbone with the addition of daratumumab. Will use the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health scale (PGH-7). The PROMIS PGH-7 has a standard deviation of 10 points, with higher scores indicating better HRQoL.
Measured: Baseline (at time of randomization) to day 64 of consolidation
Incidence of therapy-related toxicity and tolerability
Will compare therapy-related toxicity and tolerability between patients with T-ALL or T-LL randomized to a modified aBFM backbone or to a modified aBFM backbone with the addition of daratumumab. Will be assessed for all patients and the rates compared between the randomized arms (T-ALL: arm A versus (vs) arm B and T-LL: arm C vs arm D). Rates by arm will be reviewed by the study committee on a monthly basis and will also be provided in the biannual reports to the Children's Oncology Group Data and Safety Monitoring Committee for review. Any concerns regarding excessive rates of any toxicities will be discussed in the context of any required therapy modifications.
Measured: Assessed up to 3 cycles post randomization (each cycle is approximately 2-3 months)
Overall survival (OS) in patients with newly diagnosed T-ALL
Will compare OS in patients with newly diagnosed T-ALL who are randomized to either receive a modified aBFM chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab. Patients who are alive will be censored at date of last follow-up. Comparison of OS between the two randomized arms will be conducted at the time of the final analysis for the primary objective (EFS). Analyses will be based on stratified log-rank tests. In addition, descriptive OS rates post randomization will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. In particular, 4-year OS rates in arm A and arm B will be estimated. Estimation of treatment effect will be done using intent-to-treat (ITT) analysis. Hazard ratio (HR) and the confidence interval will be estimated based on Cox regression models as appropriate.
Measured: From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years
Overall survival (OS) in patients with newly diagnosed T-LL
Will compare OS in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab. Patients who are alive will be censored at date of last follow-up. Comparison of OS between the two randomized arms will be conducted at the time of the final analysis for the primary objective (EFS). Analyses will be based on log-rank tests. In addition, descriptive OS rates post randomization will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. In particular, 4-year OS rates in arm C and arm D will be estimated. Estimation of treatment effect will be done using ITT analysis. HR and the confidence interval will be estimated based on Cox regression models as appropriate.
Measured: From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start28 Aug 2026 (estimated)
- Primary completion1 Sep 2035 (estimated)
- Study completion1 Sep 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage II T Lymphoblastic Leukemia/LymphomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,708 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Keith J August, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07072585
- Sponsor's protocol ID
- AALL2331
- Other IDs
- NCI-2025-02230, AALL2331, AALL2331, U10CA180886
- Status last verified
- Jun 2026
- First submitted
- 7 May 2025
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3 Randomized Trial Investigating Daratumumab on a Modified Augmented BFM (aBFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LL)
- ClinicalTrials.gov ID
- NCT07072585
- Acronym / sponsor ID
- AALL2331
- Conditions
- Stage II T Lymphoblastic Leukemia/Lymphoma, Stage III T Lymphoblastic Leukemia/Lymphoma, Stage IV T Lymphoblastic Leukemia/Lymphoma, T Acute Lymphoblastic Leukemia, T Lymphoblastic Lymphoma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,708 participants (estimated)
- Lead sponsor
- Children's Oncology GroupResearch network
- Study start
- 28 Aug 2026 (estimated)
- Primary completion
- 1 Sep 2035 (estimated)
- Study completion
- 1 Sep 2035 (estimated)
- First posted
- 18 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with daratumumab may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To compare the event-free survival (EFS) from the end of induction (EOI) in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Münster (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab.
II. To compare the EFS from the EOI in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab.
SECONDARY OBJECTIVES:
- To compare health-related quality of life (HRQoL) and therapy-related toxicity and tolerability between patients with T-ALL or T-LL randomized to a modified aBFM backbone or to a modified aBFM backbone with the addition of daratumumab.
II. To compare overall survival (OS) from date of randomization in patients with newly diagnosed T-ALL who are randomized to either receive a modified aBFM chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab.
III. To compare OS from date of randomization in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab.
EXPLORATORY OBJECTIVES:
- In patients with newly diagnosed T-LL, to determine if minimal residual disease (MRD) testing at EOI can predict EFS and/or OS.
II. In T-ALL patients, to describe changes in the immunophenotype (specifically CD38 surface expression on T-ALL/T-LL blasts) and for the development of anti-daratumumab antibodies over the course of treatment and correlate changes with clinical outcomes and demographic variables.
III. To explore the associations between family-reported social determinants of health and both clinical outcomes (including incidence of treatment-related toxicities, EFS, OS), and leukemia/lymphoma and host biology.
IV. To describe outcome differences (EFS and OS) in patients with T-LL who differ in degrees of positron emission tomography (PET)-imaging avid disease at the EOI.
- To explore potential imaging findings and biomarkers of significant/severe nelarabine-induced central nervous system toxicities by central review of magnetic resonance imaging (MRI) and to investigate possible clinical features in patients experiencing such toxicities.
VI. To bank peripheral blood specimens for future correlative studies in patients with T-LL.
VII. To compare EFS and OS from the EOI in patients with newly diagnosed T-ALL who are MRD positive (≥ 0.01%) at the EOI to those who are MRD negative at the EOI.
OUTLINE: This is a phase II study, followed by a phase III study. Patients are assigned to 1 of 2 groups.
GROUP I T-ALL:
INDUCTION: Patients receive cytarabine intrathecally (IT) once at the time of lumbar puncture, or day 1, daunorubicin intravenously (IV) over 1 - 15 minutes on days 1, 8, 15 and 22, dexamethasone orally (PO) or IV twice a day (BID) on days 1 - 28, vincristine IV on days 1, 8, 15 and 22, pegaspargase IV over 1 - 2 hours or intramuscularly (IM) once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and methotrexate IT on days 8 and 29 (patients with central nervous system [CNS]1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 8, 15, 22 and 29 (patients with CNS3). Induction treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
EOI: Patients are randomized to 1 of 2 arms.
ARM A:
CONSOLIDATION: Patients receive nelarabine IV over 60 minutes QD on days 1 - 5 and 36 - 40, cyclophosphamide IV over 30 - 60 minutes on days 8 and 43, cytarabine IV over 1 - 30 minutes or subcutaneously (SC) QD on days 8 - 11, 15 - 18, 43 - 46 and 50 - 53, mercaptopurine PO QD on days 8 - 21 and 43 - 56, methotrexate IT on days 15, 22, 50 and 57 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 15, 22, 50 and 57 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 22 and 57 or calaspargase pegol-mknl IV over 1 - 2 hours on days 22 and 57, and vincristine IV on days 22, 29, 57 and 64. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 77 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 1% following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 0.1% following interim maintenance proceed to delayed intensification.
DELAYED INTENSIFICATION:
PART 1: Patients receive dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and vincristine IV on days 1, 8 and 15. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive nelarabine IV over 60 minutes QD on days 29 - 33, cyclophosphamide IV over 30 - 60 minutes once on day 36, cytarabine IV over 1 - 30 minutes or SC QD on days 36 - 39 and 43 - 46, thioguanine PO QD on days 36 - 49, methotrexate IT on days 36 and 43 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 36 and 43 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 50 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 50, and vincristine IV on days 50 and 57. Delayed intensification part 2 treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
CYCLES 1 - 3: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 28 and 36 - 84, prednisone PO or IV BID on days 1 - 5 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5 and 57 - 61 or methylprednisolone IV BID on days 1 - 5 and 57 - 61, vincristine IV on days 1 and 57, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78, and nelarabine IV over 60 minutes QD on days 29 - 33. Cycles repeat every 84 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 4 +: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61, mercaptopurine PO QD on days 1 - 84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days until 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
ARM B:
CONSOLIDATION: Patients receive daratumumab IV on days 8, 15, 22, 29, 43, 50, 57 and 64, nelarabine IV over 60 minutes QD on days 1 - 5 and 36 - 41, cyclophosphamide IV over 30 - 60 minutes on days 8 and 43, cytarabine IV over 1 - 30 minutes or SC QD on days 8 - 11, 15 - 18, 43 - 46 and 50 - 53, mercaptopurine PO QD on days 8 - 21 and 43 - 56, methotrexate IT on days 15, 22, 50 and 57 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 15, 22, 50 and 57 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 23 and 58 or calaspargase pegol-mknl IV over 1 - 2 hours on days 23 and 58, and vincristine IV on days 22, 29, 57 and 64. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 77 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 1% following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive daratumumab IV on days 1, 21 and 41, methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity. Patients with MRD < 0.1% following interim maintenance proceed to delayed intensification.
DELAYED INTENSIFICATION:
PART 1: Patients receive daratumumab IV on days 1 and 15, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive nelarabine IV over 60 minutes QD on days 29 - 33, daratumumab IV on days 36 and 50, cyclophosphamide IV over 30 - 60 minutes once on day 36, cytarabine IV over 1 - 30 minutes or SC QD on days 36 - 39 and 43 - 46, thioguanine PO QD on days 36 - 49, methotrexate IT on days 36 and 43 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 36 and 43 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 51 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 51, and vincristine IV on days 50 and 57. Delayed intensification part 2 treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
CYCLES 1 - 3: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 28 and 36 - 84, prednisone PO or IV BID on days 1 - 5 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5 and 57 - 61 or methylprednisolone IV BID on days 1 - 5 and 57 - 61, vincristine IV on days 1 and 57, methotrexate PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78, and nelarabine IV over 60 minutes QD on days 29 - 33. Cycles repeat every 84 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 4 +: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61, mercaptopurine PO QD on days 1 - 84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days until 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo echocardiography (ECHO) during screening and bone marrow biopsy and aspiration as well as lumbar puncture throughout the study. Patients may undergo MRI, ultrasound and biopsy on study as well as may undergo blood sample collection throughout the study.
GROUP II T-LL:
INDUCTION: Patients receive bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 8 and 11, cytarabine IT once at the time of lumbar puncture, or day 1, daunorubicin IV over 1 - 15 minutes on days 1, 8, 15 and 22, prednisone PO or IV BID on days 1 - 28 or prednisolone PO or IV BID on days 1 - 28 or methylprednisolone IV BID on days 1 - 28, methotrexate IT on days 8 and 29 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 8, 15, 22 and 29 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4, and vincristine IV on days 1, 8, 15 and 22. Induction treatment continues over 35 days in the absence of disease progression or unacceptable toxicity.
EOI: Patients are randomized to 1 of 2 arms.
ARM C:
CONSOLIDATION: Patients receive cyclophosphamide IV over 30 - 60 minutes on days 1 and 29, cytarabine IV over 1 - 30 minutes or SC QD on days 1 - 4, 8 - 11, 29 - 32 and 36 - 39, mercaptopurine PO QD on days 1 - 14 and 29 - 42, methotrexate IT on days 1, 8, 15 and 22 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1, 8, 15 and 22 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 15 and 43 or calaspargase pegol-mknl IV over 1 - 2 hours on days 15 and 43, and vincristine IV on days 15, 22, 43 and 50. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION:
PART 1: Patients receive bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 15 and 18, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive cyclophosphamide IV over 30 - 60 minutes once on day 29, cytarabine IV over 1 - 30 minutes or SC QD on days 29 - 32 and 36 - 39, thioguanine PO QD on days 29 - 42, methotrexate IT on days 29 and 36 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 29 and 36 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 43 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 43, and vincristine IV on days 43 and 50. Delayed intensification part 2 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 84, prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or methylprednisolone IV BID on days 1 - 5, 29 - 33 and 57 - 61, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days for 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
ARM D:
CONSOLIDATION: Patients receive daratumumab IV on days 1, 8, 15, 22, 29, 36, 43 and 50, cyclophosphamide IV over 30 - 60 minutes on days 1 and 29, cytarabine IV over 1 - 30 minutes or SC QD on days 1 - 4, 8 - 11, 29 - 32 and 36 - 39, mercaptopurine PO QD on days 1 - 14 and 29 - 42, methotrexate IT on days 1, 8, 15 and 22 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1, 8, 15 and 22 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM on days 16 and 44 or calaspargase pegol-mknl IV over 1 - 2 hours on days 16 and 44, and vincristine IV on days 15, 22, 43 and 50. Patients with persistent testicular disease undergo radiation therapy QD for 12 fractions within the first two weeks of consolidation. Consolidation treatment continues over 63 days in the absence of disease progression or unacceptable toxicity. Patients with a CR following consolidation proceed to interim maintenance.
INTERIM MAINTENANCE: Patients receive daratumumab IV on days 1, 21 and 41, methotrexate IT on days 1 and 31 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT on days 1 and 31 (patients with CNS3), methotrexate IV over 2 - 15 minutes on days 1, 11, 21, 31 and 41, pegaspargase IV over 1 - 2 hours or IM on days 2 and 22 or calaspargase pegol-mknl IV over 1 - 2 hours on days 2 and 23, and vincristine IV on days 1, 11, 21, 31 and 41. Interim maintenance treatment continues over 56 days in the absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION:
PART 1: Patients receive daratumumab IV on days 1 and 15, bortezomib IV over 3 - 5 seconds or SC on days 1, 4, 15 and 18, dexamethasone PO or IV BID on days 1 - 7 and 15 - 21, doxorubicin IV over 3 - 15 minutes on days 1, 8 and 15, methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), vincristine IV on days 1, 8 and 15, and pegaspargase IV over 1 - 2 hours or IM once on day 4 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 4. Delayed intensification part 1 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
PART 2: Patients receive daratumumab IV QD on days 29 and 43, cyclophosphamide IV over 30 - 60 minutes once on day 29, cytarabine IV over 1 - 30 minutes or SC QD on days 29 - 32 and 36 - 39, thioguanine PO QD on days 29 - 42, methotrexate IT QD on days 29 and 36 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT QD on days 29 and 36 (patients with CNS3), pegaspargase IV over 1 - 2 hours or IM once on day 44 or calaspargase pegol-mknl IV over 1 - 2 hours once on day 44, and vincristine IV QD on days 43 and 50. Delayed intensification part 2 treatment continues over 28 days in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive methotrexate IT once on day 1 (patients with CNS1 or CNS2) or methotrexate IT, hydrocortisone IT and cytarabine IT once on day 1 (patients with CNS3), mercaptopurine PO QD on days 1 - 84, prednisone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or prednisolone PO or IV BID on days 1 - 5, 29 - 33 and 57 - 61 or methylprednisolone IV BID on days 1 - 5, 29 - 33 and 57 - 61, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78. Cycles repeat every 84 days for 2 years from the start of interim maintenance in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo ECHO during screening and lumbar puncture as well as computed tomography (CT) or MRI, PET or PET-CT or bone scan throughout the study. Patients may undergo ultrasound and biopsy on study as well as may undergo blood sample collection and bone marrow biopsy and aspiration throughout the study.
After completion of study treatment, patients are followed up for 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group I, Arm A (T-ALL, no daratumumab) | Active comparator | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Procedure: Echocardiography Test, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Nelarabine, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Procedure: Ultrasound Imaging, Drug: Vincristine SulfateSee Detailed Description |
| Group I, Arm B (T-ALL, daratumumab) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Biological: Daratumumab, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Procedure: Echocardiography Test, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Nelarabine, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Procedure: Ultrasound Imaging, Drug: Vincristine SulfateSee Detailed Description |
| Group II, Arm C (T-LL, no daratumumab) | Active comparator | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Bone Scan, Drug: Bortezomib, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Procedure: Echocardiography Test, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Prednisolone, Drug: Prednisone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Procedure: Ultrasound Imaging, Drug: Vincristine SulfateSee Detailed Description |
| Group II, Arm D (T-LL, daratumumab) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Bone Scan, Drug: Bortezomib, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Biological: Daratumumab, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Procedure: Echocardiography Test, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Prednisolone, Drug: Prednisone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Procedure: Ultrasound Imaging, Drug: Vincristine SulfateSee Detailed Description |
Who may qualify
- Ages
- 365 days to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrolled on AALL2331.
- Patients must be > 365 days and < 21 years of age at the time of diagnosis.
- * Newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LL) stages II-IV.
Key exclusion criteria (20 listed)
- Diagnosis of Down syndrome (trisomy 21).
- Patients with known Charcot-Marie-Tooth disease.
- * Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-LL or for any cancer diagnosis prior to the initiation of protocol therapy on AALL2331 with the exception of:
- * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Bone Marrow AspirationUndergo bone marrow aspiration | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo bone marrow biopsy | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Bone ScanAlso: Bone ScintigraphyUndergo bone scan | Procedure or surgery | Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| BortezomibAlso: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, Boruzu, LDP 341, LDP-341Given IV or SC | Drug | Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Calaspargase PegolAlso: Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285Given IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518Given IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IT or IV or SC | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| DaratumumabAlso: Daratumumab Biosimilar HLX15, Daratumumab-fihj, Darzalex, HLX15Given IV | Biological | Group I, Arm B (T-ALL, daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Daunorubicin HydrochlorideAlso: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, DaunoblastinGiven IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Doxorubicin HydrochlorideAlso: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, AdriamycinGiven IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Echocardiography TestAlso: EC, EchocardiographyUndergo ECHO | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Lumbar PunctureAlso: LP, Spinal TapUnder lumbar puncture | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Mercaptopurine Oral SuspensionAlso: 6-MP Oral Suspension, Purixan, XaluprineGiven PO | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IT or IV or PO | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| MethylprednisoloneAlso: Adlone, Caberdelta M, DepMedalone, Depo ModerinGiven IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| NelarabineAlso: 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78Given IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab) |
| PegaspargaseAlso: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-AsparaginaseGiven IV or IM | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET or PET-CT | Procedure or surgery | Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| PrednisoloneAlso: (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione, .delta.1-Hydrocortisone, Adnisolone, AprednislonGiven PO or IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| PrednisoneAlso: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, CortancylGiven PO or IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Questionnaire AdministrationAncillary studies | Other | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo radiation therapy | Radiation | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Therapeutic HydrocortisoneAlso: Aeroseb-HC, Barseb HC, Barseb-HC, CetacortGiven IT | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| ThioguanineAlso: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiolGiven PO | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Ultrasound ImagingAlso: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, UltrasonographyUndergo ultrasound | Procedure or surgery | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
| Vincristine SulfateAlso: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, OncovinGiven IV | Drug | Group I, Arm A (T-ALL, no daratumumab), Group I, Arm B (T-ALL, daratumumab), Group II, Arm C (T-LL, no daratumumab), Group II, Arm D (T-LL, daratumumab) |
Primary outcome
Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL)
Time frame: From date of randomization (randomization conducted at the end of induction [EOI]) to date of first event (consolidation failure, interim maintenance failure, relapse, secondary malignant neoplasm [SMN], death from any cause), assessed up to 4 years
Will compare EFS in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Munich (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls). A phase 2/3 design will be used.
EFS in patients with newly diagnosed T-cell lymphoblastic lymphoma (T-LL)
Time frame: From date of randomization (randomization conducted at the EOI) to date of first event (consolidation failure, relapse, progressive disease, SMN, death from any cause), assessed up to 4 years
Will compare EFS in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls).
4 secondary outcomes
Health-related quality of life (HRQoL)
Time frame: Baseline (at time of randomization) to day 64 of consolidation
Incidence of therapy-related toxicity and tolerability
Time frame: Assessed up to 3 cycles post randomization (each cycle is approximately 2-3 months)
Overall survival (OS) in patients with newly diagnosed T-ALL
Time frame: From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years
Overall survival (OS) in patients with newly diagnosed T-LL
Time frame: From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Keith J August principal investigator
Children's Oncology Group
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Biopsy Procedure, Biospecimen Collection and Bone Marrow Aspiration in people with Stage II T Lymphoblastic Leukemia/Lymphoma and Stage III T Lymphoblastic Leukemia/Lymphoma, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL) (time frame: From date of randomization (randomization conducted at the end of induction [EOI]) to date of first event (consolidation failure, interim maintenance failure, relapse, secondary malignant neoplasm [SMN], death from any cause), assessed up to 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.