Blinatumomab in High-risk B-cell Precursor Acute Lymphoblastic Leukemia
Status:
Active, not recruiting
Trial end date:
2028-10-30
Target enrollment:
Participant gender:
Summary
The GRAALL-QUEST study is a Phase 2 study nested in the GRAALL-2014/B study (NCT02617004).
The GRAALL-QUEST study evaluates the safety and the efficacy of blinatumomab-containing
consolidation and maintenance therapy in patients aged 18-59 years old with high-risk B-cell
precursor acute lymphoblastic leukemia (BCP-ALL) in first complete hematologic remission
after one induction course of standard chemotherapy and no central nervous system (CNS)
involvement at diagnosis.
High-risk patients are defined as patients with KMT2A/MLL gene rearrangement, and/or IKZF1
(Ikaros) intra-genic deletion and/or high post-induction Ig-TCR minimal residual disease
(MRD) level (≥10-4). In such patients not receiving blinatumomab, 3-year hematologic relapse
incidence and relapse-free survival (RFS) are estimated at 60-65% and 50% only, respectively,
on the basis of historical results.
A large subset of these high-risk patients (i.e. those with post-induction MRD level ≥10-3
and/or post-consolidation MRD level ≥10-4), but not all, will also be considered as
candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first
hematologic remission. The primary objective of the GRAALL-QUEST study is to evaluate the
efficacy of adding blinatumomab to consolidation and eventually maintenance therapy in term
of Relapse Free Survival (RFS). Secondary objectives are overall survival, comparison of RFS
and Overall Survival (OS) in transplanted versus non-transplanted patients, MRD response and
safety. Blinatumomab will be given as monthly cycles at the daily dose of 28 microg/d
continuous IV infusion, together with 3 triple intra-thecal (IT) chemotherapy injections. The
first cycle will start after completion of the first consolidation chemotherapy phase
(corresponding to the MRD2 time-point). Patients receiving allo-HSCT will receive successive
blinatumomab cycles until allo-HSCT. Patients not receiving allo-HSCT will receive a first
blinatumomab cycle (cycle 1) during the second consolidation chemotherapy phase, followed by
late intensification, then the third consolidation chemotherapy phase including another
blinatumomab cycle (cycle 2) and maintenance chemotherapy including three additional
blinatumomab cycles (cycles 3 to 5), for a total of 5 blinatumomab cycles maximum.