Older patients with acute myeloblastic leukemia (AML). MedDRA version: 8.1 Level: PT Classification code 10000878 Term: LAM
Conditions
Interventions
Trade Name: VESANOID 10 mg
Product Name: VESANOID 10 mg
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: TRETINOINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration n
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Aged of 65 to 79 years - With a morphologically proven diagnosis of AML according to WHO classification either de novo or post -MDS - Not previously treated for AML - Signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - APL in the WHO classification. - Ph1-positive AML or prior Ph1-positive disease - AML evolving from a prior MPS in the WHO classification. - Prior treatment with chemotherapy or radiotherapy for another tumor - Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin carcinoma - Prior advanced malignant hepatic tumor - ECOG Performance Status Score > 2. - Known Poor-risk cytogenetics, including monosomy 7, abnormalities of both chromosomes 5 and 7, 3q abnormality, and complex karyotype (5 anomalies or more). - Creatinine level more than 2x's the upper limit of the normal range (ULN) at the laboratory where the analysis was performed, except if AML-related. - Total serum bilirubin more than 2x's the ULN at the laboratory where the analysis was - performed, except if AML-related. - AST (SGOT) or ALT (SGPT) more than 2.5x's the ULN at the laboratory where the analysis was performed, except if AML-related - LVEF less than.55 or equivalent by doppler echocardiography - Known intolerance to Azacitidine, mannitol, retinoids, pegfilgrastim - Positive serum test for HIV and HTLV-1 - NYHA Grade 3/4 cardiac disease . - Severe infection at inclusion time - Psychiatric disease or an history of non-compliance to medical regimens or patients considered potentially unreliable. - Absence of health care insurance (affiliation à un régime de Sécurité Sociale) - Participation to any study requiring informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Untreated AML patients aged more than 65 will be subjected to two randomizations (R1 and R2), in this study. The primary objective of the first randomization (R1) is to assess the benefit in terms of Event Free Survival (EFS) of untreated AML patients aged more than 65 years, treated with induction and consolidation chemotherapy courses, in one arm or with the same chemotherapy courses combined with ATRA in the other arm. The primary objective of the second randomization (R2) is to assess the benefit in terms of Relapse Free Interval (RFI) of maintenance with azacitidine in AML patients in CR, after induction and 4 to 6 consolidation courses of chemotherapy +/- ATRA. ;Secondary Objective: - CR rate - Overall survival - Assess the safety of combination ATRA + chemotherapy and of maintenance with azacitidine - Response rate to azacitidine +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy - Effects on relapse rates of ATRA and maintenance, with respect to cytogenetics risk groups, subtypes of AML and mutational status (FLT3, MLL), and biomarkers.;Primary end point(s): Primary endpoints: Event Free Survival (EFS), defined as the time to the first event including relapse, death, measured from randomization R1. Relapse Free Incidence (RFI), defined as 1- cumulative incidence of relapse from randomization R2, including all MDS relapses or AML relapses. Secondary endpoints: - CR rate - Cumulative incidence of relapse from CR - Overall survival - Response and safety of the following combinations : ATRA + chemotherapy, azacitidine or azacitidine + ATRA after induction failure. - Safety and toxicity of maintenance with azacitidine - Possible predictors to response to ATRA, azacitidine after failure: with respect to cytogenetics. risk groups, diagnosis groups 1 and 2, mutational status (NPM, FLT3, MLL) and biomarkers. - Predictors of prolonged RFI in maintenance ar | — |
Countries
France
Outcome results
None listed