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NCT Number: NCT03709719

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Acute Lymphoblastic Leukemia, Adult B-Cell Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

18 year–59 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hopital saint Louis

Paris, 75010, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Included in GRAALL-2014/B
  • Whose blood and bone marrow explorations have been completed before the steroids prephase
  • 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
  • Whose karyotype shows no t(9;22) and/or the absence in molecular biology of BCR-ABL marker
  • With Eastern Cooperative Oncology Group (ECOG) performance status < 3
  • With or without central nervous system (CNS) or testis involvement
  • 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
  • Having signed a written informed consent
  • With efficient contraception for women of childbearing age (excluding estrogens and IUS)
  • With health insurance coverage
  • 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
  • Aspartate transaminase (AST) (SGOT) and/or alanine transaminase (ALT) (SGPT) ≥ 5 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • Creatinine ≥ 1.5 x ULN or creatinine clearance < 50 ml/min
  • 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)

Treatment and study plan

Blinatumomab Injection

Drug

Blinatumomab 28 μg/day : D1 to D28

Primary outcomes

  1. Disease Free Survival Y3

    Time frame: 3 years

    Disease Free Survival at 3 years

Secondary outcomes

  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

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study 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

Acronym: GRAALL-QUEST

Important dates

Study start
2018
Primary completion
2026
Study completion
2028
First posted
Oct 17, 2018
Registry last updated
May 3, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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