Multicenter Study of Risk-adapted Treatment for T-lineage ALL of Young Adults (18-59 Years Old)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of nelarabine-based consolidation and maintenance therapy in term of relapse-free survival (RFS) in high-risk (HR) patients.

Official Title
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Multicenter Study of Risk-adapted Treatment for T-lineage ALL of Young Adults (18-59 Years Old): Evaluating the Efficacy of a Nelarabine Based Consolidation and Maintenance in High-risk Patients

Conditions
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T-cell Adult Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: nelarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Whose blood and bone marrow explorations have been completed before the steroids prephase aged 18-59 years old with a not previously treated (including IT injection) T-ALL newly-diagnosed according to the WHO 2008 definition with > 20% bone marrow blasts With Eastern Cooperative Oncology Group (ECOG) performance status < 3 With or without central nervous system (CNS) involvement or testis Without other evolving cancer (except basal cell carcinoma of the skin and in situ carcinoma of the cervix) or its chemo or radio-therapy treatment finished at least since 6 months Having signed a written informed consent With efficient contraception for women of childbearing age (excluding estrogens and IUD) Having received or being receiving steroid prephase With health insurance coverage Exclusion Criteria: With lymphoblastic lymphoma and bone marrow blasts < 20%, Burkitt-type ALL or with antecedents of chronic myeloid leukemia (CML) or other myeloproliferative neoplasm 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 > 1.5 x upper limit of normal range (ULN) or creatinine clearance <50 mL/mn Myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy (NYHA grade III or IV), left ejection ventricle fraction (LEVF) < 50% and/or RF < 30%, Active severe infection or known seropositivity for HIV or Human T cell leukemia/lymphoma virus type 1 (HTLV-1) or active hepatitis B or C Other active malignancy Pregnant (beta-Human Chorionic Gonadotropin (hCG) positive) or nursing woman Women of 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 Treated with any other investigational agent or participation in another trial within 30 days prior to entering this study Not able to bear with the procedures or the frequency of visits planned in the trial Unable to consent, under tutelage or curators, or judiciary safeguard

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Risk (HR) patients<br>Nelarabine during consolidation and maintenance | Drug: nelarabine<br>* Nelarabine 1500 mg/m2/d (IV 2h) : D1, D3, D5 Cyclophosphamide 150 mg/m2/d (IV 3h) : D1, D3 etoposide (VP-16) 75 mg/m2/d (IV 1h) : D1, D3 granulocyte-colony stimulating factor 5 µg/kg/d (SC) : D7 until neutrophil >1 Giga/Liter for a maximum of 5 blocks<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 4 years | 
| Cumulative incidence of relapse |  | 4 years | 
| Non relapse mortality (NRM) |  | 4 years | 
| Disease free survival censored at allograft in first complete remission (CR) |  | 4 years | 
| Cumulative incidence of relapse censored at allograft in first complete remission (CR) |  | 4 years | 
| Overall survival censored at allograft in first complete remission (CR) |  | 4 years | 
| Non relapse mortality (NRM) censored at allograft in first complete remission (CR) |  | 4 years | 
| Minimal residual disease (MRD) |  | within 1 year | 
| Proportion of patients having received the 5 cycles of nelarabine |  | 3 years |