A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral lenalidomide to standard induction therapy in AML and RAEB ≥ 66 years and very poor risk AML ≥ 18 years

Study scheme
 

Study Objective

This study is performed in two parts; during the first part (part A) the feasible dose level of lenalidomide will be selected. The second part (part B) will continue with the selected dose level of lenalidomide.

Primary objectives

- For part A of the study (if applicable):
1. To assess the safety and tolerability of lenalidomide added to standard induction chemotherapy for AML and select the feasible dose level for part B.
2. Comparison on the CR (Complete Remission) rate of Lenalidomide added to standard induction chemotherapy versus standard induction chemotherapy alone.

- For part B:
1. To assess the safety and tolerability of the selected dose level of lenalidomide added to standard induction chemotherapy.
2. Comparison on the CR rate of the selected dose of Lenalidomide added to standard induction chemotherapy versus standard induction chemotherapy alone.

Secondary objectives

For part B:

1. To determine the efficacy profile (event free survival (EFS) disease free survival (DFS) and overall survival (OS)) associated with the two therapy regimens.
2. To measure MRD (Minimal Residual Disease) by immunophenotyping in relation to clinical response parameters.
3. To identify potential biomarkers predictive of response, EFS, DFS and OS by exploratory genomic analysis (microarray, gene mutations).

Participation conditions

Inclusion criteria

- Patients eligible for standard chemotherapy.

- Patients

≥ 66 years with a cytopathologically confirmed diagnosis according WHO classification of: AML (not APL) or refractory anemia with excess of blasts (RAEB) with an IPSS score ≥ 1.5

OR

≥ 18 years with a cytopathologically confirmed diagnosis according WHO classification of AML with very poor risk AML.

- Subjects with secondary AML progressing from antecedent (at least 4 months duration) myelodysplasia are also eligible.

- SGOT (AST) and SGPT (ALT) ≤ 1.5 x the upper limit of the normal range (ULN) at the laboratory where the analyses were performed.

- Total serum bilirubin level ≤1.5 x the ULN at the laboratory where the analysis was performed.

- Serum creatinine concentration ≤ 1.5 x the ULN at the laboratory where the analysis was performed.

- WHO performance status ≤ 2.

- Written informed consent.

- Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.

- Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion criteria

- Acute promyelocytic leukemia.

- Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (< 2 weeks) with Hydroxyurea is allowed.

- Past or current history (within the last 2 years prior to randomization) of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix.

- Blast crisis of chronic myeloid leukemia.

- Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤6 months prior to randomization), myocardial infarction (≤ 6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure.

- Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.

- Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.

- Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.

- Pregnant or lactating patients.

- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.

Centre Hospitalier de Luxembourg - CHL (Dr Laurent Plawny)