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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22
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.
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
Northwestern
Chicago, Illinois, United States
RECRUITINGComplete 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 29
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
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.
Time frame: 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..
Time frame: 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..
Time frame: 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.
Time frame: Day 29
MRD Relapse
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Time frame: 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.
Time frame: Day 64
MRD Relapse
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
Time frame: 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).
Time frame: 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).
Time frame: Day 64