Patients with de novo acute lymphoblastic leukemia of young adults. -GRAALL-2014/B: Ph- B lineage ALL -GRAALL-2014/T et ATRIALL: T-ALL -GRAAPH-2014: ALL Ph+ MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Atriance
Product Name: Atriance
Product Code: Nélarabine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Nélarabine
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General 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 ALL (including intrathecal injections) newly diagnosed according to the WHO 2008 definition with > or = 20% bone marrow blasts 3. 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 4. With ECOG =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Principal criteria: 1. Myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy, LEVF 5 x ULN b.Total bilirubin >or= 2.5 x ULN c.Creatinine >1.5 x ULN or creatinine clearance 5 x ULN b.Total bilirubin >or= 2.5 x ULN c.Creatinine >1.5 x ULN or creatinine clearance or = 3 after consolidation 1 2. With CNS disease at diagnosis, or symptomatic CNS disease, or uncontrolled epilepsy 3. With peripheral neuropathy grade >or= 2 after consolidation 1 4. With abnormal laboratory values as defined below after consolidation 1 a. AST and/or ALT >or= 5 x ULN b. Total bilirubin >or= 1.5 x ULN c. Creatinine >or= 1.5 x ULN or creatinine clearance or= 1.5 x ULN 5. With active uncontrolled infection, any other concurrent disease or medical conditionthat is deemed to interfere with the conduct of the study as judged by the investigator 6. With childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter 7. With known hypersensitivity to nelarabine GRAAPH-2014: 1. Previously treated with Tyrosine Kinase Inhibitor 2. With another active malignancy 3. With general or visceral contra-indication to intensive therapy (except if considered related to the ALL): a. ASAT and/or ALAT>or= 2.5 x ULN b. Total bilirubin >1.5 x ULN c. Creatinine >1.5 x ULN or creatinine clearance <50 mL/mn d. Se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To improve the results of our pediatric-inspired approach for patients with B-lineage Ph-negative ALL, T-lineage ALL or Ph+ ALL. For this purpose, we will consider the characteristics of ALL (using the new risk classification system) as well as age-related toxicities in order to improve tolerance. -GRAALL-2014/B: To prospectively validate the new risk model, based on MRD1 response level and KMT2A (=MLL) and IKZF1 gene status -GRAALL-2014/T: To prospectively validate the new risk factors based on MRD1 response level and NOTCH1/FBXW7/RAS/PTEN gene status. ATRIALL substudy : To evaluate the efficacy of nelarabine-based consolidation and maintenance therapy in term of RFS in HR patients -GRAAPH-2014: Non-inferiority of the experimental arm (arm B) compared to the control arm (arm A) in terms of Major Molecular Response (MMolR) after the 4th cycle (MRD4);Secondary Objective: -GRAALL-2014/B and QUEST: Evaluate the level of MRD by Ig-TCR (to demonstrate the non inferiority of DFS at 4 years by comparison to the historical group (<60%)) -GRAALL-2014/Tet ATRIAL: Appreciate the toxicity of nelarabine-in consolidation, followed by allo-SCT or further consolidation and maintenance therapy; Evaluate MRD level, monitored by Ig-TCR; Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM); Relapse-free survival (RFS) and overall survival (OS); RFS, CIR, NRM and OS after censoring at SCT in first CR -GRAAPH-2014: Comparison of the experimental arm and of the control arm in terms of tolerance, CIR, EFS and OS;Primary end point(s): -GRAALL-2014/B : Disease free survival (DFS) at 4 years, depending on the status of KMT2A (=MLL) and IKZF1 genes and on MRD1 assessed after the induction cure or on D1 of consolidation 1 -GRAALL-2014/T et ATRIALL : Analysis of the new risk factors based on MRD1 response level and NOTCH1/FBXW7/RAS/PTEN gene status by comparing the historical results of GRAALL-2005 with those of GRAALL-2014 in an identical population ( T-lineage | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): GRAALL-2014/B: Cumulative incidence of relapse (CIR) at 4 years and non-relapse related mortality (NRM), DFS, CIR, NRM and OS after censoring at allo-SCT in first CR, MRD follow-up at different treatment times (cf infra § MRD monitoring). GRAALL-2014/T: Overall survival, Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM), DFS, CIR, NRM and OS after censoring at SCT in first CR, Evaluation of nelarabine toxicity, Proportion of patients having received the 5 cycles of nelarabine. MRD follow-up at various times of treatment (cf infra § MRD monitoring). GRAAPH-2014: Tolerance Complete remission after cycle 1, Cumulative incidence of treatment- and transplantation-related mortality, Cumulative incidence of relapse, Relapse free survival, Event free survival, Overall survival, Investigation of T315I mutation and of resistance (mutations will be assessed by RQ-PCR sequencing in case of progression or relapse).;Timepoint(s) of evaluation of this end point: . | — |
Countries
Belgium, France, Switzerland
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed