Multicenter Study of Risk-adapted Treatment for T-lineage ALL of Young Adults (18-59 Years Old) (GRAALL-2014/T)

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

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.

Study Overview

• Status: Recruiting
• Conditions: T-cell Adult Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: nelarabine

• Study Type: Interventional
• Enrollment (Anticipated): 275
• Phase: Phase 2

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
    • Hematology
    • Contact: Hervé Dombret, MDPhD; 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

Description

Inclusion Criteria:

1. Whose blood and bone marrow explorations have been completed before the steroids prephase
2. 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
3. With Eastern Cooperative Oncology Group (ECOG) performance status < 3
4. With or without central nervous system (CNS) involvement or testis
5. 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
6. Having signed a written informed consent
7. With efficient contraception for women of childbearing age (excluding estrogens and IUD)
8. Having received or being receiving steroid prephase
9. With health insurance coverage

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 > 1.5 x 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 ejection ventricle fraction (LEVF) < 50% and/or RF < 30%,
4. 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
5. Other active malignancy
6. Pregnant (beta-Human Chorionic Gonadotropin (hCG) positive) or nursing woman
7. 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
8. Treated with any other investigational agent or participation in another trial within 30 days prior to entering this study
9. Not able to bear with the procedures or the frequency of visits planned in the trial
10. Unable to consent, under tutelage or curators, or judiciary safeguard

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Risk (HR) patients; Nelarabine during consolidation and maintenance	Drug: nelarabine; 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

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
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• 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: December 1, 2015
• First Posted (Estimate): December 2, 2015

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: AOM12629_2