A Multicenter, Single-arm Phase II Study to Assess the Safety, Tolerability, and Efficacy of Isatuximab in Adult Patients With Cytologic or Molecular Relapsed/Refractory CD38 Positive T-cell Acute Lymphoblastic Leukemia (GMALL-Isatuximab)
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.
∙ Cohort 1:
• 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
• after at least three chemotherapy cycles (induction I-II, consolidation I) with the following additional specifications:
‣ early relapse within 12 months from first achievement of CR or
⁃ late relapse later than 12 months from first achievement of CR or
⁃ primary refractory disease without any CR or
⁃ any relapse after stem cell transplantation or
⁃ any refractory relapse, defined as no response to at least one salvage therapy or
• any second or later relapse and
• Availability of patient material with blast cells (bone marrow or peripheral blood) for central MRD assessment or availability of respective predefined marker (not required in patients with extramedullary disease only).
• ECOG status: 0-2
• Age ≥ 18 years
• Evidence of a personally signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study
• Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Regeneration from last chemotherapy defined as follows:
‣ Platelets ≥10.000/uL (platelet transfusion allowed)
⁃ Hemoglobin ≥ 7.5 g/dl (red blood cell transfusion allowed)
• Adequate liver function defined as follows:
‣ Bilirubin ≤ 1.5 ULN (unless Gilbert Meulengracht disease or classified as result of liver infiltration by investigator)
⁃ AST and ALT ≤ 2.5 x ULN (unless classified as result of liver infiltration by investigator)
• Adequate renal function defined as follows:
‣ Serum creatinine ≤ 2 x ULN
⁃ Any serum creatinine level associated with a calculated creatinine clearance ≥ 40 mL/min
• Negative pregnancy test in women of childbearing potential (WOCBP)
• WOCBP must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously.
• Men who are sexually active with a WOCBP must agree to use a barrier method of contraception
• Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)
∙ Cohort 2:
∙ • terminated with protocol version 3.2.