Multicenter Trial Treatment of Philadelphia Chromosome Negative B-cell Acute Lymphoblastic Leukemia of Young Adults (GRAALL-2014/B)

Multicenter Trial Treatment of Philadelphia Chromosome Negative (Ph-) B-lineage Acute Lymphoblastic Leukemia (ALL) of Young Adults (18-59 Years).

The purpose of this study is to prospectively validate the new risk model, based on minimal residual disease (MRD) response level and oncogenetic status by comparing historical results of GRAALL-2005 with those of GRAALL-2014 in an identical population of patients (Philadelphia chromosome negative, B lineage ALL, aged 18 to 59 years old).

Study Overview

• Status: Recruiting
• Conditions: Philadelphia Chromosome Negative Adult B-cell Acute Lymphoblastic Leukemia

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Hervé Dombret, MDPhD; Phone Number: +33 (0)1 57 27 68 47; Email: herve.dombret@aphp.fr
• Study Contact Backup: Name: Véronique Lhéritier; Phone Number: +33(0)4 78 86 22 39; Email: veronique.lheritier@chu-lyon.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Hématologie Adulte, Saint Louis hospital
    • Contact: Hervé Dombret; Phone Number: +33 (0)1 57 27 68 47; Email: herve.dombret@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Young Adults (age 18-59) with Philadelphia Chromosome Negative B-cell Acute Lymphoblastic Leukemia

Description

Inclusion Criteria:

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 (including intrathecal injection) B-lineage-ALL 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 breakpoint cluster region-Abelson (BCR-ABL)
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 radiotherapy or chemotherapy 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 IUD)
9. With health insurance coverage
10. Who have received or being receiving the steroid prephase

Exclusion Criteria:

1. With lymphoblastic lymphoma and bone marrow blasts < 20%, Burkitt-type ALL, or with antecedents of chronic myeloid leukemia (CML) or other myeloproliferative neoplasm

2. With contra-indication to anthracyclines or any other general or visceral contra-indication to intensive therapy except if considered related to the ALL:

   • Aspartate transaminase (AST) and/or alanine transaminase (ALT) > 5 x upper limit of normal range (ULN)
   • Total bilirubin ≥ 2.5 x upper limit of normal range (ULN)
   • Creatinine >1.5x upper limit of normal range (ULN) or creatinine clearance <50 mL/mn
3. Myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy (NYHA grade III or IV), left ventricle ejection fraction (LVEF) < 50% and or Shortening fraction < 30%,
4. Active severe infection or known seropositivity for HIV or human T cell leukemia/lymphoma virus type 1 (HTLV1) or active hepatitis B or C
5. Pregnant (beta-Human Chorionic Gonadotropin positive) or nursing woman
6. Not able to bear with the procedures or the frequency of visits planned in the trial
7. Unable to consent, under tutelage or curators, or judiciary safeguard.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival (DFS)	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Minimal residual disease (MRD)	1 year
Overall survival	4 years
Cumulative incidence of relapse (CIR)	4 years
non relapse mortality (NMR)	4 years
Cumulative incidence of relapse (CIR) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)	4 years
overall survival after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)	4 years
Non relapse mortality (NRM) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)	4 years
Disease free survival (DFS) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)	4 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Hervé Dombret, MDPhD, APHP

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 27, 2015
• First Posted (Estimate): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome
• Other Study ID Numbers: AOM12629_3