Blinatumomab in High-risk B-cell Precursor Acute Lymphoblastic Leukemia (GRAALL-QUEST)
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|ClinicalTrials.gov Identifier: NCT03709719|
Recruitment Status : Active, not recruiting
First Posted : October 17, 2018
Last Update Posted : May 3, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia, Adult B-Cell||Drug: Blinatumomab Injection||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||95 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study to Evaluate the Safety and the Efficacy of a Blinatumomab Based Consolidation and Maintenance in Patients With High-risk B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL). GRAALL-QUEST|
|Actual Study Start Date :||October 20, 2018|
|Estimated Primary Completion Date :||October 30, 2026|
|Estimated Study Completion Date :||October 30, 2028|
Drug: Blinatumomab Injection
Blinatumomab 28 μg/day : D1 to D28
- Disease Free Survival Y3 [ Time Frame: 3 years ]Disease Free Survival at 3 years
- OS Y3 [ Time Frame: 3 years ]Overall survival at 3 years
- CIR Y3 [ Time Frame: 3 years ]Cumulative incidence of relapse at 3 years
- NRM [ Time Frame: 3 years ]Non Relapse related Mortality
- MRD1 [ Time Frame: after induction or on day 1 of first consolidation ]Minimal Residual Disease
- MRD2 [ Time Frame: on day 1 of second consolidation ]Minimal Residual Disease
- MRD3 [ Time Frame: on day 1 of late intensification(or at pre Allo-SCT evaluation) ]Minimal Residual Disease
- MRD4 [ Time Frame: on day 1 of maintenance phase (or at day 100 after Allo-SCT) ]Minimal Residual Disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03709719
|Hopital saint Louis|
|Paris, France, 75010|