T-ALL (T-acute lymphoblastic leukemia) is an aggressive blood cancer, wherein patients who are MRD positive after two courses of induction chemotherapy have poor outcomes. This goal of this study is to determine if Daratumumab can make such T-ALL patients MRD negative.
The main questions this study aims to answer are -
1. Whether MRD Positive T-ALL patients can become MRD negative after two doses of daratumumab? 2. Whether MRD Positive T-ALL patients can become MRD negative after four doses of daratumumab? 3. Whether addition of daratumumab can affect the risk of progression or death at 1-year? 4. Whether daratumumab is safe to use?
Newly diagnosed patients of T-ALL who are MRD positive after two courses of induction chemotherapy will be eligible to receive daratumumab. These patients will receive two doses of weekly intravenous daratumumab at standard dose (16mg/kg), and will undergo repeat evaluation of MRD from bone marrow one week after the second dose of daratumumab. Patients who become MRD negative will continue chemotherapy as per institutional policy. Those who remain MRD positive will be eligible to receive two additional doses, and will undergo another bone marrow MRD testing one week after the fourth dose. Irrespective of the results after the fourth dose, patients will be continued on chemotherapy as per institutional policy.
Adults ≥18 - ≤65 years of age
Baseline diagnosis of T-ALL, including ETP-ALL
MRD positive (≥0.01%) disease (by flow-cytometry) assessed on BM after two phases of induction chemotherapy in CR-1
CD38 positive
T-LBL (T-lymphoblastic lymphoma) without BM involvement
Patients with persistently positive CSF cytology after two phases of induction or baseline testicular involvement
Patients with symptomatic obstructive airway disease, as per assessing clinician
Presence of an active systemic infection, as per assessing clinician
Single group
Daratumumab Injection
DrugPatients will receive intravenous daratumumab (16mg/kg per dose) once weekly for 2 doses. After 2 doses, they will undergo bone marrow examination for flow-cytometric MRD. Those who become MRD negative (less than 0.01% by flow-cytometry), will be off-study and continued on conventional treatment regimen as per institution policy. Hence, total duration in those who become MRD negative will be 3 weeks. However, those who are still MRD positive (more than or equal to 0.01% by flowcytometry) after two doses, will be given two additional once weekly doses of intravenous daratumumab (16mg/kg per dose). In patients who receive two additional doses, bone marrow aspirate for MRD analysis will be done 7 days after fourth dose of daratumumab. Irrespective of MRD result after fourth dose, patients will be continued on conventional treatment regimen
MRD negativity
To determine the MRD negativity rates after two doses of weekly intravenous daratumumab as a single agent for MRD positive T-ALL
To determine cumulative incidence of MRD negativity
To determine cumulative incidence of MRD negativity with upto 4 doses of daratumumab monotherapy
Progression free survival
To determine progression free survival at 1 year
Adverse events
To determine incidence of adverse events (as per CTCAE v5.0 2017) after daratumumab therapy
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