T-Lymphocytic Leukemia, AcutePhase 2DARATALL-VHRNCT06253637
Daratumumab in VHR T-ALL Treated According to the ALL National Treatment Program
A Phase 2 study testing Daratumumab plus chemotherapy according to the national treatment program in people with T-Lymphocytic Leukemia, Acute, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 3 sites in Italy.
Trial summary
The goal of this clinical trial is to test daratumumab in adult very high risk T-lineage lymphoblastic leukemia. The main question it aims to answer is wether the addition of daratumumab daratumumab to the national standard of care is able to increase the rate of MRD-negative patients after induction therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- T-Lymphocytic Leukemia, Acute
- What is being tested?
- Daratumumab plus chemotherapy according to the national treatment program
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesItaly
- Study dates
- 17 Oct 2024to Oct 2029
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65 years.
- A diagnosis of T-ALL according to the 2022 International Consensus Classification (ICC) is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids +/- cyclophosphamide in patients presenting with hyperleukocytosis is allowed.
- Availability of fresh bone marrow (BM) (or peripheral blood (PB) in patients with hyperleukocytosis) samples to perform diagnostic procedures. ).
- Bone marrow blast percentage at diagnosis ≥20%.
- CD38 positivity on ALL blasts (any level of positivity).
- ETP and near ETP at diagnosis according to internationally accepted criteria (appendix G) at diagnosis or other VHR T-ALL subtypes (WBC count >100 x109/L; complex karyotype with ≥5 unrelated anomalies; other CD1a-negative immunophenotypes). T-Myeloid MPAL according to the 2022 ICC of Acute Leukemias of Ambiguous Lineage (appendix H) can also be eligible and considered as VHR.
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- Availability of full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications.
- An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.
- For females of childbearing potential, a negative pregnancy test must be documented. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.
- Signed written informed consent according to ICH/E U/GCP and national local laws.
Who cannot join
- Diagnosis of B-lineage ALL, and Ph+ ALL.
- Down's syndrome.
- Prior systemic chemotherapy for ALL (excluding cyclophosphamide during pre-phase).
- Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum direct bilirubin >3 mg/dL (unless attributable to Gilbert' syndrome or ALL) and/or ALT >5x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
- Presence of serious, active, uncontrolled infections.
- A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with a life expectancy <2 years.
- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Ematologia AOU Careggi
Florence
Ematologia P.O. Vito Fazzi - Lecce
Lecce
Ematologia AOU Policlinico Umberto I
Roma
About this study
Official title: Daratumumab in Very High-Risk T-Lineage Acute Lymphoblastic Leukemia (ALL) Treated According to the ALL National Treatment Program (DARATALL-VHR)
The goal of this clinical trial is to test daratumumab in adult very high risk T-lineage lymphoblastic leukemia.
The main question it aims to answer is wether the addition of daratumumab daratumumab to the national standard of care is able to increase the rate of MRD-negative patients after induction therapy.
Participants will be treated with:
- daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.
Read the detailed description
This study is a multicenter phase II trial based on the addition of daratumumab to chemotherapy in the front-line treatment of very high-risk T-ALL.
T-ALL patients are eligible at diagnosis in case of ETP or near ETP immunophenotype. Due to their biological and clinical similarities, T-Myeloid MPAL can also be included. Other VHR T-ALL patients (i.e. those with WBC count >100 x109/L, with complex karyotype with ≥5 unrelated anomalies or with a CD1a-negative immunophenotype) will also be eligible.
A safety run-in is foreseen for 5 patients: if grade >3 infusion-related reactions or extra hematologic adverse events of grade >3 that, for investigator's clinical judgement cannot be due to chemotherapy alone, are not observed in more than 2 patients during the first cycle of daratumumab, the study will continue with the core phase.
After a steroid/cyclophosphamide pre-treatment phase, that can occur before enrollment during the screening period, patients who meet the eligibility criteria will be treated with daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.
- Conditions
- T-Lymphocytic Leukemia, Acute
- Being tested
- Daratumumab plus chemotherapy according to the national treatment program
- 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 plus chemotherapy according to the national treatment programDrug
Daratumumab is a human IgG1қ monoclonal antibody that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein which is expressed in several hematological malignancies including multiple myeloma (MM) and ALL. Daratumumab induces lysis of CD38-expressing tumor cells by several mechanisms. Intravenous daratumumab has been approved first as a single agent and then in combinations in the MM setting and in AL amyloidosis.
The activity of daratumumab in ALL is being explored in the DELPHINUS trial, in which the drug was combined with chemotherapy in pediatric and young adult patients with relapsed/refractory T-cell ALL or lymphoblastic lymphoma (LL).
In the present trial, daratumumab will be administered to adult Very high risk T-lineage ALL weekly in induction and early consolidation (C1-C2), and the first day of each of the following intensive cycles up to C8.
| Study group | Role | What they receive |
|---|---|---|
| Very high risk T-ALL patients treated with daratumumab and the national treatment program | Experimental | After a steroid/cyclophosphamide pre-treatment phase, patients will be treated according to the national treatmetn program - as per the previous GIMEMA LAL1913 - plus daratumumab as follows:
* In the first cycle, C1, daratumumab (subcutaneous) 1800 mg will be administered on days 1, 8, 15 and 22
* In the second cycle, C2, daratumumab 1800 mg will be administered on days 1, 8, 15
* In the subsequent cycles C3-C8 daratumumab 1800 mg will be administered on day 1
in addition to chemotherapy according to the national treatment program
Induction/consolidation cycles are administered at 28 (C1-2) and 21(C2-8) day intervals. Dose reductions are required in patients > 55y
All patients are eligible for allo-SCT after C3. All patients unable to undergo an allo-SCT are eligible for an auto-SCT after C8, If unable to undergo an auto-SCT, these patients are eligible to maintenance at the end of the consolidation program. Receives: Drug: Daratumumab plus chemotherapy according to the national treatment program |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRD-negativity rate after cycle 1
Number of patients on the total of evaluable patients without residual disease after the first induction cycle with chemotherapy plus daratumumab
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2024
- Study start17 Oct 2024
- Primary completionOct 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for T-Lymphocytic Leukemia, AcuteStudies 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
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sabina Chiaretti, Principal investigator, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06253637
- Sponsor's protocol ID
- ALL3024
- Acronym
- DARATALL-VHR
- Status last verified
- Mar 2026
- First submitted
- 2 Feb 2024
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daratumumab in Very High-Risk T-Lineage Acute Lymphoblastic Leukemia (ALL) Treated According to the ALL National Treatment Program (DARATALL-VHR)
- ClinicalTrials.gov ID
- NCT06253637
- Acronym / sponsor ID
- DARATALL-VHR / ALL3024
- Conditions
- T-Lymphocytic Leukemia, Acute
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- 17 Oct 2024 (actual)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 12 Feb 2024 (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.
The goal of this clinical trial is to test daratumumab in adult very high risk T-lineage lymphoblastic leukemia.
The main question it aims to answer is wether the addition of daratumumab daratumumab to the national standard of care is able to increase the rate of MRD-negative patients after induction therapy.
Participants will be treated with:
- daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.
Detailed description
This study is a multicenter phase II trial based on the addition of daratumumab to chemotherapy in the front-line treatment of very high-risk T-ALL.
T-ALL patients are eligible at diagnosis in case of ETP or near ETP immunophenotype. Due to their biological and clinical similarities, T-Myeloid MPAL can also be included. Other VHR T-ALL patients (i.e. those with WBC count >100 x109/L, with complex karyotype with ≥5 unrelated anomalies or with a CD1a-negative immunophenotype) will also be eligible.
A safety run-in is foreseen for 5 patients: if grade >3 infusion-related reactions or extra hematologic adverse events of grade >3 that, for investigator's clinical judgement cannot be due to chemotherapy alone, are not observed in more than 2 patients during the first cycle of daratumumab, the study will continue with the core phase.
After a steroid/cyclophosphamide pre-treatment phase, that can occur before enrollment during the screening period, patients who meet the eligibility criteria will be treated with daratumumab in combination with a pediatric-inspired treatment scheme - as in the previous GIMEMA LAL1913 protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Very high risk T-ALL patients treated with daratumumab and the national treatment program | Experimental | Drug: Daratumumab plus chemotherapy according to the national treatment programAfter a steroid/cyclophosphamide pre-treatment phase, patients will be treated according to the national treatmetn program - as per the previous GIMEMA LAL1913 - plus daratumumab as follows: * In the first cycle, C1, daratumumab (subcutaneous) 1800 mg will be administered on days 1, 8, 15 and 22 * In the second cycle, C2, daratumumab 1800 mg will be administered on days 1, 8, 15 * In the subsequent cycles C3-C8 daratumumab 1800 mg will be administered on day 1 in addition to chemotherapy according to the national treatment program Induction/consolidation cycles are administered at 28 (C1-2) and 21(C2-8) day intervals. Dose reductions are required in patients > 55y All patients are eligible for allo-SCT after C3. All patients unable to undergo an allo-SCT are eligible for an auto-SCT after C8, If unable to undergo an auto-SCT, these patients are eligible to maintenance at the end of the consolidation program. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18-65 years.
- A diagnosis of T-ALL according to the 2022 International Consensus Classification (ICC) is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids +/- cyclophosphamide in patients presenting with hyperleukocytosis is allowed.
- Availability of fresh bone marrow (BM) (or peripheral blood (PB) in patients with hyperleukocytosis) samples to perform diagnostic procedures. ).
- Bone marrow blast percentage at diagnosis ≥20%.
- CD38 positivity on ALL blasts (any level of positivity).
Key exclusion criteria (7 listed)
- Diagnosis of B-lineage ALL, and Ph+ ALL.
- Down's syndrome.
- Prior systemic chemotherapy for ALL (excluding cyclophosphamide during pre-phase).
- Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum direct bilirubin >3 mg/dL (unless attributable to Gilbert' syndrome or ALL) and/or ALT >5x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
- Presence of serious, active, uncontrolled infections.
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 plus chemotherapy according to the national treatment programDaratumumab is a human IgG1қ monoclonal antibody that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein which is expressed in several hematological malignancies including multiple myeloma (MM) and ALL. Daratumumab induces lysis of CD38-expressing tumor cells by several mechanisms. Intravenous daratumumab has been approved first as a single agent and then in combinations in the MM setting and in AL amyloidosis. The activity of daratumumab in ALL is being explored in the DELPHINUS trial, in which the drug was combined with chemotherapy in pediatric and young adult patients with relapsed/refractory T-cell ALL or lymphoblastic lymphoma (LL). In the present trial, daratumumab will be administered to adult Very high risk T-lineage ALL weekly in induction and early consolidation (C1-C2), and the first day of each of the following intensive cycles up to C8. | Drug | Very high risk T-ALL patients treated with daratumumab and the national treatment program |
Primary outcome
MRD-negativity rate after cycle 1
Time frame: 1 month
Number of patients on the total of evaluable patients without residual disease after the first induction cycle with chemotherapy plus daratumumab
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 5 Mar 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Sabina Chiaretti principal investigator
University of Roma La Sapienza
3 sites 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 plus chemotherapy according to the national treatment program in people with T-Lymphocytic Leukemia, Acute, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 3 sites in Italy.
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 10 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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?
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?
MRD-negativity rate after cycle 1 (time frame: 1 month). 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 5 Mar 2026.