The planned trial offers treatment cohorts for patients with full cytologic relapse (R/R ALL - Cohort 1), as well as for patients with molecular failure/relapse (MRD+ ALL - Cohort 2). Basically, the study aims to develop data for optimization of first-line therapy of T-ALL, either by modification of standard induction with Isatuximab or by establishing a post-induction therapy for eradication of MRD and thereby evaluates in parallel two different strategies.
Patients with CD38 positive T-ALL/T-LBL
Either: In relapse or with primary refractory disease defined as ≥5% blasts in bone marrow cytology or ≥1% minimal residual disease (MRD)
Or: Extramedullary relapse or primary refractory disease confirmed by standard imaging with measurable target leasions
early relapse within 12 months from first achievement of CR or
Patients with CNS-only relapse
Patients who have received prior antileukemic immunotherapy within 2 weeks prior to start of Isatuximab treatment
Patients who have received treatment for leukemia with chemotherapy within 2 weeks prior to start of Isatuximab treatment (exception: documented disease progression under chemotherapy and pre-phase therapy with 5-7 days of Dexamethasone, 3 days of Cyclophosphamide; intrathecal prophylaxis)
Patients who are candidates for a treatment with Nelarabine (eligibility to be assessed particularly in patients with extramedullary involvement and/or early/mature T-ALL/T-LBL, due to limited efficacy)
Single group
Isatuximab
DrugCohort 1: All patients will receive two cycles of induction therapy with standard chemotherapy, Bortezomib and Isatuximab. Isatuximab maintenance may be administered in patients with CR until SCT, progression/relapse, unacceptable toxicity, physicians' decision to change treatment or withdrawal of consent.
Isatuximab
DrugCohort 2: All patients will receive at least one cycle with Isatuximab. Each cycle will be 4 weeks in duration. Isatuximab will be administered until SCT, hematologic relapse including extramedullary, unacceptable toxicity, physicians' decision, or withdrawal of consent - terminated with protocol version 3.2.
Proportion of patients with complete hematologic response (ORR= CR and CRi)
Cohort 1: Proportion of patients with complete hematologic response (ORR= CR and CRi) after 2 cycles of induction therapy including Isatuximab.
Overall incidence and severity of adverse events
Cohort 1: Overall incidence and severity of adverse events (CTCAE 5.0).
Proportion of patients with molecular response (MolCR)
Cohort 2: Proportion of patients with molecular response (MolCR) after one cycle of Isatuximab.
Proportion of patients with CR and CRi, MolCR and cMolCR in R/R
Cohort 1: Proportion of patients with CR and CRi, MolCR and cMolCR in R/R (cohort 1) after 1 or 2 cycles of induction (best response)
Probability of continuous complete remission
Probability of continuous complete remission (remission duration) at 18 months
Probability of overall survival
Probability of overall survival at 18 months
Probability of relapse-free survival
Probability of relapse-free survival at 18 months
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Goethe University
Lead sponsor
Sanofi
Collaborator
