Blinatumomab in High-risk B-cell Precursor Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia, Adult B-Cell Clinical Trial

— GRAALL-QUEST  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03709719
• Other study ID #: GRAALL-QUEST
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 20, 2018
• Est. completion date: October 30, 2028

Study information

• Verified date: April 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 95
• Est. completion date: October 30, 2028
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, Adult B-Cell
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blinatumomab Injection
Blinatumomab 28 µg/day : D1 to D28

Locations

Country	Name	City	State
France	Hopital saint Louis	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival Y3	Disease Free Survival at 3 years	3 years
Secondary	OS Y3	Overall survival at 3 years	3 years
Secondary	CIR Y3	Cumulative incidence of relapse at 3 years	3 years
Secondary	NRM	Non Relapse related Mortality	3 years
Secondary	MRD1	Minimal Residual Disease	after induction or on day 1 of first consolidation
Secondary	MRD2	Minimal Residual Disease	on day 1 of second consolidation
Secondary	MRD3	Minimal Residual Disease	on day 1 of late intensification(or at pre Allo-SCT evaluation)
Secondary	MRD4	Minimal Residual Disease	on day 1 of maintenance phase (or at day 100 after Allo-SCT)