Clinical trial NCT02617004: Multicenter Trial Treatment of Philadelphia Chromosome Negative B-cell Acute Lymphoblastic Leukemia of Young Adults
Official title: Multicenter Trial Treatment of Philadelphia Chromosome Negative (Ph-) B-lineage Acute Lymphoblastic Leukemia (ALL) of Young Adults (18-59 Years).
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Philadelphia Chromosome Negative Adult B-cell Acute Lymphoblastic Leukemia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-11-30
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Young Adults (age 18-59) with Philadelphia Chromosome Negative B-cell Acute Lymphoblastic Leukemia

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: 4 years
Secondary outcomes:
measure: Cumulative incidence of relapse (CIR)
timeFrame: 4 years
measure: non relapse mortality (NMR)
timeFrame: 4 years
measure: Overall survival
timeFrame: 4 years
measure: Cumulative incidence of relapse (CIR) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)
timeFrame: 4 years
measure: overall survival after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)
timeFrame: 4 years
measure: Non relapse mortality (NRM) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)
timeFrame: 4 years
measure: Disease free survival (DFS) after censoring at allo-stem cell transplantation (SCT) in first complete remission (CR)
timeFrame: 4 years
measure: Minimal residual disease (MRD)
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Hématologie Adulte, Saint Louis hospital
Study officials:
affiliation: APHP
name: Hervé Dombret, MDPhD
role: PRINCIPAL_INVESTIGATOR
References: