Blinatumomab in High-risk B-cell Precursor Acute Lymphoblastic Leukemia (GRAALL-QUEST)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia, Adult B-Cell
• Intervention / Treatment: Drug: Blinatumomab Injection

• Study Type: Interventional
• Enrollment (Anticipated): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hopital Saint Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: blinatumomab	Drug: Blinatumomab Injection; Blinatumomab 28 μg/day : D1 to D28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival Y3	Disease Free Survival at 3 years	3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2018
• Primary Completion (Anticipated): October 30, 2026
• Study Completion (Anticipated): October 30, 2028

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: GRAALL-QUEST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No