Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03709719
Recruitment Status : Active, not recruiting
First Posted : October 17, 2018
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia, Adult B-Cell Drug: Blinatumomab Injection Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: blinatumomab Drug: Blinatumomab Injection
Blinatumomab 28 μg/day : D1 to D28




Primary Outcome Measures :
  1. Disease Free Survival Y3 [ Time Frame: 3 years ]
    Disease Free Survival at 3 years


Secondary Outcome Measures :
  1. OS Y3 [ Time Frame: 3 years ]
    Overall survival at 3 years

  2. CIR Y3 [ Time Frame: 3 years ]
    Cumulative incidence of relapse at 3 years

  3. NRM [ Time Frame: 3 years ]
    Non Relapse related Mortality

  4. MRD1 [ Time Frame: after induction or on day 1 of first consolidation ]
    Minimal Residual Disease

  5. MRD2 [ Time Frame: on day 1 of second consolidation ]
    Minimal Residual Disease

  6. MRD3 [ Time Frame: on day 1 of late intensification(or at pre Allo-SCT evaluation) ]
    Minimal Residual Disease

  7. MRD4 [ Time Frame: on day 1 of maintenance phase (or at day 100 after Allo-SCT) ]
    Minimal Residual Disease



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

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


Locations
Layout table for location information
France
Hopital saint Louis
Paris, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03709719    
Other Study ID Numbers: GRAALL-QUEST
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blinatumomab
Antineoplastic Agents