NCT05289687 · Eastern Cooperative Oncology Group
Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Daratumumab / Hyaluronidase Injection
Daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22
DRUG
Daratumumab / Hyaluronidase Injection
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.
DRUG
Daratumumab / Hyaluronidase Injection
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
DRUG
Daratumumab / Hyaluronidase Injection
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.
Primary outcome measures
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).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
- 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.
Exclusion criteria
- -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
Where
- Chicago, Illinois
Collaborators
Janssen, LP
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 17, 2026 · Source of record for eligibility and locations