T-cell Acute Lymphoblastic LeukemiaPhase 2NCT05289687
Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL
A Phase 2 study testing Daratumumab / Hyaluronidase Injection in people with T-cell Acute Lymphoblastic Leukemia, run by Eastern Cooperative Oncology Group at 1 site in United States.
Trial summary
In this study, the investigators are hypothesizing that daratumumab-hyaluronidase will effectively treat T-ALL in patients who have persistent or recurrent MRD following treatment with chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- T-cell Acute Lymphoblastic Leukemia
- What is being tested?
- Daratumumab / Hyaluronidase Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 25 May 2023to 30 Jun 2027
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have documented T cell ALL and must be in first or later hematologic CR or CRi after a minimum of 2 blocks of intensive chemotherapy.
- Patients in hematologic CR or CRi must have persistent or recurrent MRD ≥ 10-4.
- Institution must have received central MRD status test results confirming persistent or recurrent MRD ≥ 10-4 by flow cytometry.
- Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have Grafts Versus Host Disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is ≤ 10 mg per day.
- Patient must have an ECOG performance status 0-2.
- All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy.
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- Patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue to 3 months after the last dose of protocol treatment. Patients must also agree to abstain from donating sperm, even if they have had a successful vasectomy, or donating eggs while on study treatment and for 3 months after the last dose of protocol treatment.
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
- Patient must have adequate organ and marrow function as defined below (these labs must be obtained ≤ 7 days prior to Step 1 registration).
- Absolute neutrophil count (ANC) ≥ 750/μL
- Platelets ≥ 75,000/μL
- Total or Direct bilirubin ≤ 2 mg/dL
- AST(SGOT)/ALT(SGPT) ≤ 3.0 × institutional ULN
- Creatinine ≤ 1.5 x institutional ULN or Creatinine Clearance > 30 ml/min
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Patients with prior CNS involvement are eligible as long as they do not have active CNS involvement at time of Step 1 registration.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
Who cannot join
- -Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northwestern
Chicago, Illinois, 60611
Shira Dinner, MD, 312-695-2120, shira.dinner@nm.org
About this study
Official title: A Phase II Study of Daratumumab-Hyaluronidase for Chemotherapy-Relapsed/Refractory Minimal Residual Disease (MRD) in T Cell Acute Lymphoblastic Leukemia (T-ALL
In this study, the investigators are hypothesizing that daratumumab-hyaluronidase will effectively treat T-ALL in patients who have persistent or recurrent MRD following treatment with chemotherapy.
Read the detailed description
The primary hypothesis is that daratumumab-hyaluronidase will effectively eliminate chemotherapy refractory and relapsed MRD in T-ALL. The secondary hypotheses include; daratumumab-hyaluronidase will improve hematologic relapse free survival (RFS),daratumumab-hyaluronidase will improve overall survival (OS), patients that achieve complete MRD response with daratumumab will have improved survival outcomes, and daratumumab-hyaluronidase will be well tolerated in T-ALL after allogenic stem cell transplant.
The primary objective of this study is to evaluate the rate of complete MRD response by flow cytometry after 4 weekly doses of daratumumab-hyaluronidase (Day 29) among patients with MRD positive T-ALL in hematologic morphologic complete remission or complete remission with incomplete hematologic recovery. The secondary objectives include; evaluation of morphologic relapse free survival (RFS), evaluation of overall survival (OS), assessment of the the survival outcomes in patients that undergo allogeneic stem cell transplant after complete MRD response with daratumumab-hyaluronidase, assessment of adverse effects and tolerability of daratumumab-hyaluronidase in T-ALL, and assessment of flow cytometry based MRD status on Day 64 of treatment or upon count recovery for patients that receive chemotherapy in addition to daratumumab-hyaluronidase during Course 1A.
- Conditions
- T-cell Acute Lymphoblastic Leukemia
- Being tested
- Daratumumab / Hyaluronidase Injection
- Medical subject headings
- 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.
Daratumumab / Hyaluronidase InjectionDrug
Daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22
Daratumumab / Hyaluronidase InjectionDrug
Patients that are MRD Negative on Day 29 will receive daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57.
Daratumumab / Hyaluronidase InjectionDrug
Patients that remain MRD positive on Day 29 will receive a combination of daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57 and chemotherapy selected from the combinations listed below:
- Cytarabine 3000 mg/m2, IV, Every 12 hours for 4 doses on Days 37 and 38
- Methotrexate 1000 mg/m2, IV, Over 24 hours on Day 36
OR
- Methotrexate, Starting dose 100 mg/m2, IV, Days 36, 46, 56
- Vincristine, 1.5 mg/m2 (2 mg cap), IV, Days 36, 46, 56
- Pegaspargase, 2000 IU/m2 (Capped at 3750 IU), IV Days 37, 57
- Methotrexate 15 mg, IT, Days 36, 56
Daratumumab / Hyaluronidase InjectionDrug
All patients with MRD negative response after completion of previous course are eligible for daratumumab-hyaluronidase 1800mg/ 30,000 units every 2 weeks on Days 1,15, 29, 43, 57, 71, 85, and 99 for 8 doses.
| Study group | Role | What they receive |
|---|---|---|
| Course 1 | Experimental | Daratumumab-hyaluronidase Receives: Drug: Daratumumab / Hyaluronidase Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR)
Requires that all of the following be present.
- Peripheral Blood Counts
- Neutrophil count ≥ 1,000/µL.
- Platelet count ≥ 100,000/µL.
- Reduced hemoglobin concentration or hematocrit has no bearing on remission status.
- Leukemic blasts must not be present in the peripheral blood.
- Bone Marrow Aspirate and Biopsy
- Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines.
- ≤ 5% T lymphoblasts by flow cytometry.
- Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
Measured: Day 29
Complete Remission (CR)
Requires that all of the following be present.
- Peripheral Blood Counts
- Neutrophil count ≥ 1,000/µL.
- Platelet count ≥ 100,000/µL.
- Reduced hemoglobin concentration or hematocrit has no bearing on remission status.
- Leukemic blasts must not be present in the peripheral blood.
- Bone Marrow Aspirate and Biopsy
- Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines.
- ≤ 5% T lymphoblasts by flow cytometry.
- Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
Measured: Day 64
Complete Response with Partial Count Recovery (CRh)
The same as for CR except with unsupported platelets > 50,000/μL, hemoglobin > 7 g/dL, and absolute neutrophil count > 500/μL.
Measured: Day 29
Complete Response with Partial Count Recovery (CRh)
The same as for CR except with unsupported platelets > 50,000/μL, hemoglobin > 7 g/dL, and absolute neutrophil count > 500/μL.
Measured: Day 64
Complete Remission incomplete (CRi)
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets > 75,000/uL but < 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery > 750/uL but < 1000/μL.
Measured: Day 29
Complete Remission incomplete (CRi)
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets > 75,000/uL but < 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery > 750/uL but < 1000/μL.
Measured: Day 64
Minimal Residual Disease Negativity (MRD-)
Bone marrow lymphoblast percent < 0.01% (< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
Measured: Day 29
Minimal Residual Disease Negativity (MRD-)
Bone marrow lymphoblast percent < 0.01% (< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
Measured: Day 64
Morphologic Relapse
Bone Marrow Aspirate and Biopsy
- Presence of > 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration).
- If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
Measured: Day 29
MRD Relapse
- Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Measured: Day 29
Morphologic Relapse
Bone Marrow Aspirate and Biopsy
- Presence of > 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration).
- If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
Measured: Day 64
MRD Relapse
- Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Measured: Day 64
Refractory
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
Measured: Day 29
Refractory
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
Measured: Day 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2022
- Study start25 May 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for T-cell Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single arm study of daratumumab-hyaluronidase in T-ALL patients in morphologic CR with persistent or relapsed MRD. MRD will be assessed centrally for eligibility and response by flow cytometry. All patients will receive daratumumab-hyaluronidase once weekly for up to 4 doses during Course 1. .
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eastern Cooperative Oncology Group
- Sponsor type
- Research network
- Collaborators
- Janssen, LP
- Responsible party
- Sponsor
- Investigators
- Shira Dinner, MD, Study chair, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05289687
- Sponsor's protocol ID
- EA9213
- Status last verified
- Sep 2026
- First submitted
- 18 Feb 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012 Jan 5;119(1):34-43. doi: 10.1182/blood-2011-04-347872. Epub 2011 Nov 15.
PubMed 22086414Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.
PubMed 22412151Steinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, Johnstone HS, Sather HN, Trigg ME, Uckun FM, Bleyer WA. Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. Cancer. 1998 Feb 1;82(3):600-12. doi: 10.1002/(sici)1097-0142(19980201)82:33.0.co;2-4.
PubMed 9452280Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. doi: 10.1182/blood-2009-08-231217.
PubMed 19828704Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schafer BW, Arico M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-84. doi: 10.1182/blood-2011-03-338707. Epub 2011 Jun 30.
PubMed 21719599Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cave H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lheritier V, Bene MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014 Jun 12;123(24):3739-49. doi: 10.1182/blood-2014-01-547695. Epub 2014 Apr 16.
PubMed 24740809Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J, Luschen S, Pott C, Ritgen M, Scheuring U, Horst HA, Thiel E, Hoelzer D, Bartram CR, Kneba M; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006 Feb 1;107(3):1116-23. doi: 10.1182/blood-2005-07-2708. Epub 2005 Sep 29.
PubMed 16195338Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, Fietkau R, Freund M, Ganser A, Ludwig WD, Maschmeyer G, Rieder H, Schwartz S, Serve H, Thiel E, Bruggemann M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012 Aug 30;120(9):1868-76. doi: 10.1182/blood-2011-09-377713. Epub 2012 Mar 22.
PubMed 22442346Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013 Sep;162(5):606-20. doi: 10.1111/bjh.12442. Epub 2013 Jun 29.
PubMed 23808872Brent L. Wood, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Si Chen, Barbara Asselin, Natia Esiashvili, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz SPH. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early Thymic precursor (ETP) Immunophenotype, and validation of the prognostic value of end- induction minimal residual disease (MRD) in Children's oncology group (COG) Study AALL0434 Blood 2014;124.
Wood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. Patients with early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) have high levels of minimal residual disease (MRD) at the end of induction-a Children's oncology group (COG) study [abstract]. Blood. 2009;114.
Quist-Paulsen P, Toft N, Heyman M, Abrahamsson J, Griskevicius L, Hallbook H, Jonsson OG, Palk K, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Opdahl S, Marquart HV, Siitonen S, Osnes LT, Hultdin M, Overgaard UM, Wartiovaara-Kautto U, Schmiegelow K. T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol. Leukemia. 2020 Feb;34(2):347-357. doi: 10.1038/s41375-019-0598-2. Epub 2019 Oct 14.
PubMed 31611626Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22.
PubMed 29358182Bride KL, Vincent TL, Im SY, Aplenc R, Barrett DM, Carroll WL, Carson R, Dai Y, Devidas M, Dunsmore KP, Fuller T, Glisovic-Aplenc T, Horton TM, Hunger SP, Loh ML, Maude SL, Raetz EA, Winter SS, Grupp SA, Hermiston ML, Wood BL, Teachey DT. Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia. Blood. 2018 Mar 1;131(9):995-999. doi: 10.1182/blood-2017-07-794214. Epub 2018 Jan 5.
PubMed 29305553Vogiatzi F, Winterberg D, Lenk L, Buchmann S, Cario G, Schrappe M, Peipp M, Richter-Pechanska P, Kulozik AE, Lentes J, Bergmann AK, Valerius T, Frielitz FS, Kellner C, Schewe DM. Daratumumab eradicates minimal residual disease in a preclinical model of pediatric T-cell acute lymphoblastic leukemia. Blood. 2019 Aug 22;134(8):713-716. doi: 10.1182/blood.2019000904. Epub 2019 Jul 16. No abstract available.
PubMed 31311816
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Daratumumab-Hyaluronidase for Chemotherapy-Relapsed/Refractory Minimal Residual Disease (MRD) in T Cell Acute Lymphoblastic Leukemia (T-ALL
- ClinicalTrials.gov ID
- NCT05289687
- Acronym / sponsor ID
- EA9213
- Conditions
- T-cell Acute Lymphoblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Eastern Cooperative Oncology GroupResearch network
- Collaborators
- Janssen, LP
- Study start
- 25 May 2023 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 21 Mar 2022 (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.
In this study, the investigators are hypothesizing that daratumumab-hyaluronidase will effectively treat T-ALL in patients who have persistent or recurrent MRD following treatment with chemotherapy.
Detailed description
The primary hypothesis is that daratumumab-hyaluronidase will effectively eliminate chemotherapy refractory and relapsed MRD in T-ALL. The secondary hypotheses include; daratumumab-hyaluronidase will improve hematologic relapse free survival (RFS),daratumumab-hyaluronidase will improve overall survival (OS), patients that achieve complete MRD response with daratumumab will have improved survival outcomes, and daratumumab-hyaluronidase will be well tolerated in T-ALL after allogenic stem cell transplant.
The primary objective of this study is to evaluate the rate of complete MRD response by flow cytometry after 4 weekly doses of daratumumab-hyaluronidase (Day 29) among patients with MRD positive T-ALL in hematologic morphologic complete remission or complete remission with incomplete hematologic recovery. The secondary objectives include; evaluation of morphologic relapse free survival (RFS), evaluation of overall survival (OS), assessment of the the survival outcomes in patients that undergo allogeneic stem cell transplant after complete MRD response with daratumumab-hyaluronidase, assessment of adverse effects and tolerability of daratumumab-hyaluronidase in T-ALL, and assessment of flow cytometry based MRD status on Day 64 of treatment or upon count recovery for patients that receive chemotherapy in addition to daratumumab-hyaluronidase during Course 1A.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm study of daratumumab-hyaluronidase in T-ALL patients in morphologic CR with persistent or relapsed MRD. MRD will be assessed centrally for eligibility and response by flow cytometry. All patients will receive daratumumab-hyaluronidase once weekly for up to 4 doses during Course 1. .
| Arm | Type | Receives |
|---|---|---|
| Course 1 | Experimental | Drug: Daratumumab / Hyaluronidase InjectionDaratumumab-hyaluronidase |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient must have documented T cell ALL and must be in first or later hematologic CR or CRi after a minimum of 2 blocks of intensive chemotherapy.
- Patients in hematologic CR or CRi must have persistent or recurrent MRD ≥ 10-4.
- Institution must have received central MRD status test results confirming persistent or recurrent MRD ≥ 10-4 by flow cytometry.
- Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have Grafts Versus Host Disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is ≤ 10 mg per day.
- Patient must have an ECOG performance status 0-2.
Key exclusion criteria (1 listed)
- -Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
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 |
|---|---|---|
| Daratumumab / Hyaluronidase InjectionDaratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22 | Drug | Course 1 |
| Daratumumab / Hyaluronidase InjectionPatients that are MRD Negative on Day 29 will receive daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57. | Drug | Course 1 |
| Daratumumab / Hyaluronidase InjectionPatients that remain MRD positive on Day 29 will receive a combination of daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57 and chemotherapy selected from the combinations listed below: * Cytarabine 3000 mg/m2, IV, Every 12 hours for 4 doses on Days 37 and 38 * Methotrexate 1000 mg/m2, IV, Over 24 hours on Day 36 OR * Methotrexate, Starting dose 100 mg/m2, IV, Days 36, 46, 56 * Vincristine, 1.5 mg/m2 (2 mg cap), IV, Days 36, 46, 56 * Pegaspargase, 2000 IU/m2 (Capped at 3750 IU), IV Days 37, 57 * Methotrexate 15 mg, IT, Days 36, 56 | Drug | Course 1 |
| Daratumumab / Hyaluronidase InjectionAll patients with MRD negative response after completion of previous course are eligible for daratumumab-hyaluronidase 1800mg/ 30,000 units every 2 weeks on Days 1,15, 29, 43, 57, 71, 85, and 99 for 8 doses. | Drug | Course 1 |
Primary outcome
Complete Remission (CR)
Time frame: Day 29
Requires that all of the following be present. * Peripheral Blood Counts * Neutrophil count ≥ 1,000/µL. * Platelet count ≥ 100,000/µL. * Reduced hemoglobin concentration or hematocrit has no bearing on remission status. * Leukemic blasts must not be present in the peripheral blood. * Bone Marrow Aspirate and Biopsy * Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines. * ≤ 5% T lymphoblasts by flow cytometry. * Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
Complete Remission (CR)
Time frame: Day 64
Requires that all of the following be present. * Peripheral Blood Counts * Neutrophil count ≥ 1,000/µL. * Platelet count ≥ 100,000/µL. * Reduced hemoglobin concentration or hematocrit has no bearing on remission status. * Leukemic blasts must not be present in the peripheral blood. * Bone Marrow Aspirate and Biopsy * Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines. * ≤ 5% T lymphoblasts by flow cytometry. * Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
Complete Response with Partial Count Recovery (CRh)
Time frame: Day 29
The same as for CR except with unsupported platelets > 50,000/μL, hemoglobin > 7 g/dL, and absolute neutrophil count > 500/μL.
Complete Response with Partial Count Recovery (CRh)
Time frame: Day 64
The same as for CR except with unsupported platelets > 50,000/μL, hemoglobin > 7 g/dL, and absolute neutrophil count > 500/μL.
Complete Remission incomplete (CRi)
Time frame: Day 29
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets > 75,000/uL but < 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery > 750/uL but < 1000/μL.
Complete Remission incomplete (CRi)
Time frame: Day 64
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets > 75,000/uL but < 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery > 750/uL but < 1000/μL.
Minimal Residual Disease Negativity (MRD-)
Time frame: Day 29
Bone marrow lymphoblast percent < 0.01% (< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
Minimal Residual Disease Negativity (MRD-)
Time frame: Day 64
Bone marrow lymphoblast percent < 0.01% (< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
Morphologic Relapse
Time frame: Day 29
Bone Marrow Aspirate and Biopsy * Presence of > 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration). * If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
MRD Relapse
Time frame: Day 29
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Morphologic Relapse
Time frame: Day 64
Bone Marrow Aspirate and Biopsy * Presence of > 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration). * If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
MRD Relapse
Time frame: Day 64
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Refractory
Time frame: Day 29
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
Refractory
Time frame: Day 64
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
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 15 Sep 2026.
- Background: PubMed 22086414Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012 Jan 5;119(1):34-43. doi: 10.1182/blood-2011-04-347872. Epub 2011 Nov 15.
- Background: PubMed 22412151Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.
- Background: PubMed 9452280Steinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, Johnstone HS, Sather HN, Trigg ME, Uckun FM, Bleyer WA. Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. Cancer. 1998 Feb 1;82(3):600-12. doi: 10.1002/(sici)1097-0142(19980201)82:33.0.co;2-4.
- Background: PubMed 19828704Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. doi: 10.1182/blood-2009-08-231217.
- Background: PubMed 21719599Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schafer BW, Arico M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-84. doi: 10.1182/blood-2011-03-338707. Epub 2011 Jun 30.
- Background: PubMed 24740809Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cave H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lheritier V, Bene MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014 Jun 12;123(24):3739-49. doi: 10.1182/blood-2014-01-547695. Epub 2014 Apr 16.
- Background: PubMed 16195338Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J, Luschen S, Pott C, Ritgen M, Scheuring U, Horst HA, Thiel E, Hoelzer D, Bartram CR, Kneba M; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006 Feb 1;107(3):1116-23. doi: 10.1182/blood-2005-07-2708. Epub 2005 Sep 29.
- Background: PubMed 22442346Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, Fietkau R, Freund M, Ganser A, Ludwig WD, Maschmeyer G, Rieder H, Schwartz S, Serve H, Thiel E, Bruggemann M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012 Aug 30;120(9):1868-76. doi: 10.1182/blood-2011-09-377713. Epub 2012 Mar 22.
- Background: PubMed 23808872Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013 Sep;162(5):606-20. doi: 10.1111/bjh.12442. Epub 2013 Jun 29.
- BackgroundBrent L. Wood, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Si Chen, Barbara Asselin, Natia Esiashvili, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz SPH. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early Thymic precursor (ETP) Immunophenotype, and validation of the prognostic value of end- induction minimal residual disease (MRD) in Children's oncology group (COG) Study AALL0434 Blood 2014;124.
- BackgroundWood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. Patients with early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) have high levels of minimal residual disease (MRD) at the end of induction-a Children's oncology group (COG) study [abstract]. Blood. 2009;114.
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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.
Shira Dinner, MD study chair
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab / Hyaluronidase Injection in people with T-cell Acute Lymphoblastic Leukemia, run by Eastern Cooperative Oncology Group at 1 site in United States.
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 20 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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?
Contact Shira Dinner, MD (312-695-6180, shira.dinner@nm.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission (CR) (time frame: Day 29). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05289687, which also lists 24 linked publications.
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 15 Sep 2026.