A Randomized Phase II Study of Clofarabine / Intermediate-Dose Cytarabine (CLARA)versus High-Dose Cytarabine (HDAC) as Consolidation in Younger Patients with Newly-Diagnosed Acute Myeloid Leukemia (AML). - CLARA

Phase 1

• Conditions: Acute Myeloid Leukemia; MedDRA version: 9.1Level: LLTClassification code 10000886Term: Acute myeloid leukemia

• Registration Number: EUCTR2008-000668-18-FR
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-12
• Last Update Posted: 4 July 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Age 18 years or more and less than 60 years.
2.With:
A morphologically proven diagnosis of AML according to the WHO classification, cytogenetically (standard karyotype, FISH-MLL) and molecularly (FLT3, CEBPA, NMP1) defined.
3.ECOG performance status 0 to 2.
4.Serum creatinine ? 2N; AST and ALT ? 2.5N; total bilirubin ? 2N (unless related to the underlying disease).
5.Cardiac function determined by radionucleide or echography within normal limits.
6.Women of child-bearing potential (i.e. women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods, and must have a negative serum or urine pregnancy test within 2 weeks prior the beginning treatment on this trial.
7.Must be able and willing to give written informed consent.
8.The subject must be covered by a social security system.

At randomization:
•Patients with either in first CR/CRp after the first induction course or in first CR/CRp after salvage therapy.
•ECOG performance status 0 to 2.
•Serum creatinine ? 2N; AST and ALT ? 2.5N; total bilirubin ? 2N.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients with AML with favorable risk cytogenetics: M3-AML; CBF-AML including t(8:21), inv(16), or t(16;16) AML.
2.Ph-positive AML.
3.AML following diagnosed myeloproliferation or patient with prior history of MDS known for more than 3 months
4.Prior treatment with chemotherapy or radiotherapy for another tumor.
5.Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin carcinoma
6.Performance Status Score ECOG > 2.
7.Compromised organ function judged to be lifethreatening by the Investigator.
8.Positive serology for HIV, HBV and HBC (except post vaccination)
9.Uncontrolled active infection of any kind or bleeding. Patients with infections who are under active treatment with antibiotics and whose infections are controlled may be entered to the study.
10.Other active malignancy.
11. Patents concurrently receiving any other standard or investigational treatment for their leukemia, with the exception of hydroxyurea.

At randomization:
•Absence of CR or CRp after induction chemotherapy or induction plus salvage chemotherapy.
•Patients belonging to the intermediate 1 risk group (CEBPA+ or NPM1+ without Flt3-ITD) in CR/CRp after the first induction course.These patients will go out of the study and receive consolidation cycles based on HD-AraC.
•Performance Status Score ECOG > 2.
•Known central nervous system involvement with AML.
•Uncontrolled active infection of any kind or bleeding.
•Compromized organ function judged to be lifethreatening by the Investigator.
•Patients scheduled and waiting for allogeneic stem cell transplantation (see Appendix 4). The idea is that no randomized patient should receive allogeneic stem cell transplantation after randomization.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 2 years diease free survival following first remission achievement (CR or CRp) in younger patients with intermediate-risk or unfavorable-risk AML;Secondary Objective: •Safety profile of CLARA versus HDAC consolidation courses.<br>•Possible predictors to response: with respect to cytogenetics risk groups and mutational status (FLT3, MLL, CEBPA and NPM).<br>•Minimal residual disease level after 2 courses of consolidation.<br>•Relationship between minimal residual disease and relapse of AML.<br>•Overall cumulative incidence of relapse at 120 days.<br>•Overall survival at 2 years.<br>;Primary end point(s): The intent-to-treat population will include all patients who have been randomized for consolidation chemotherapy. All efficacy and safety analyses will be performed on the intention-to-treat population. The primary efficacy endpoint is disease-free survival (DFS) at 2 years, defined as the time to the first event including relapse, death, and measured from randomization.