Description:
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.
Title
- Brief Title: Blinatumomab in High-risk B-cell Precursor Acute Lymphoblastic Leukemia
- 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
Clinical Trial IDs
- ORG STUDY ID:
GRAALL-QUEST
- NCT ID:
NCT03709719
Conditions
- Acute Lymphoblastic Leukemia, Adult B-Cell
Interventions
| Drug | Synonyms | Arms |
|---|
| Blinatumomab Injection | | blinatumomab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| blinatumomab | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Included in GRAALL-2014/B
1. Whose blood and bone marrow explorations have been completed before the steroids
prephase
2. Aged 18 to 59 years old with not previously treated B-lineage-ALL (including
intrathecal injections) newly diagnosed according to the WHO 2008 definition with
> 20% bone marrow blasts
3. Whose karyotype shows no t(9;22) and/or the absence in molecular biology of
BCR-ABL marker
4. With Eastern Cooperative Oncology Group (ECOG) performance status < 3
5. With or without central nervous system (CNS) or testis involvement
6. Without other evolving cancer (except basal cell carcinoma of the skin or "in
situ" carcinoma of the cervix) or its treatment should be finished at least since
6 months
7. Having signed a written informed consent
8. With efficient contraception for women of childbearing age (excluding estrogens
and IUS)
9. With health insurance coverage
10. Who have received or being receiving the steroid prephase
- With High Risk (HR) B-ALL
- ECOG ≤ 3
- In Complete Remission after one or two induction cures and having received the three
blocks of consolidation N°1
- With or without allogeneic donor
Exclusion Criteria:
- With ECOG status > 3 after consolidation 1
- With abnormal laboratory values as defined below after consolidation 1
1. Aspartate transaminase (AST) (SGOT) and/or alanine transaminase (ALT) (SGPT) ≥ 5
x ULN
2. Total bilirubin ≥ 1.5 x ULN
3. Creatinine ≥ 1.5 x ULN or creatinine clearance < 50 ml/min
4. Serum amylase and lipase ≥ 1.5 x ULN
- With active uncontrolled infection, any other concurrent disease or medical condition
that is deemed to interfere with the conduct of the study as judged by the
investigator
- New York Heart Association (NYHA) Functional Classification 3-4 cardiac disease
- Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis
B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
| Maximum Eligible Age: | 59 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Disease Free Survival Y3 |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Disease Free Survival at 3 years |
Secondary Outcome Measures
| Measure: | OS Y3 |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Overall survival at 3 years |
| Measure: | CIR Y3 |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Cumulative incidence of relapse at 3 years |
| Measure: | NRM |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Non Relapse related Mortality |
| Measure: | MRD1 |
| Time Frame: | after induction or on day 1 of first consolidation |
| Safety Issue: | |
| Description: | Minimal Residual Disease |
| Measure: | MRD2 |
| Time Frame: | on day 1 of second consolidation |
| Safety Issue: | |
| Description: | Minimal Residual Disease |
| Measure: | MRD3 |
| Time Frame: | on day 1 of late intensification(or at pre Allo-SCT evaluation) |
| Safety Issue: | |
| Description: | Minimal Residual Disease |
| Measure: | MRD4 |
| Time Frame: | on day 1 of maintenance phase (or at day 100 after Allo-SCT) |
| Safety Issue: | |
| Description: | Minimal Residual Disease |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Assistance Publique - Hôpitaux de Paris |
Last Updated
May 3, 2021
