Randomized study with a run-in dose-selection phase to assess the added value of lenalidomide in combination with standard remission-induction chemotherapy and post-remission treatment in patients aged 18-65 years with previously untreated acute myeloid leukemia (AML) or high risk myelodysplasia (MDS) (IPSS-R risk score > 4.5)

• Conditions: previously untreated acute myeloid leukemia (AML) or high risk myelodysplasie (MDS); MedDRA version: 18.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 18.1Level: LLTClassification code 10028532Term: MyelodysplasiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-002843-26-NL
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-13
• Last Update Posted: 14 December 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 927

Inclusion Criteria

- Age 18-65 years, inclusive
- Patients with
- a diagnosis of AML and related precursor neoplasms according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML), or
- acute leukemia’s of ambiguous lineage according to WHO 2008 or
- a diagnosis of refractory anemia with excess of blasts (MDS) and IPSS-R score > 4.5
- WHO performance status 0, 1 or 2
- Sampled bone marrow and/ blood cells for centralized molecular analysis and MRD evaluation, unless in case of a dry marrow tap with no possibility to collect marrow cells. In cases of marrow tap failure only blood cells will be sampled.
- Adequate renal and hepatic functions as indicated by the following laboratory values:
- Serum creatinine =1.0 mg/dL (=88.7 µmol/L); if serum creatinine >1.0 mg/dL (>88.7 µmol/L), then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m^2) = 186 x (Serum Creatinine in mg/dL)^-1.154 x (age in years)^-0.203 x (0.742 if patient is female) x (1.212 if patient is black)
NOTE: if serum creatinine is measured in umol/L, recalculate it in mg/dL according to the equation: 1 mg/dL = 88.7 umol/L) and use above mentioned formula.
- Serum bilirubin =2.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST) = 2.5 x ULN
- Alanine transaminase (ALT) = 2.5 x ULN
- Alkaline phosphatase = 2.5 x ULN
- Written informed consent
- Ability to adhere to the lenalidomide Pregnancy Prevention Program

Part B:
- CR or CRi
- Absolute neutrophil count (ANC) = 1.5 x 10^9/L
- Platelet count = 75 x 10^9/L
- Serum creatinine clearance = 30 ml/min or estimated glomerular filtration rate (GFR) > 60mL/min/1.73 m^2
- Total bilirubin = 2.5 x ULN
- AST = 2.5 x ULN
- ALT = 2.5 x ULN

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 871
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

- Previous therapy with lenalidomide
- Acute promyelocytic leukemia
- Myeloproliferative neoplasia
- Previous treatment for AML or high risk MDS (IPSS-R > 4.5), except hydroxyurea
- Concurrent history of active malignancy in two past years prior to diagnosis except for:
- basal and squamous cell carcinoma of the skin
- in situ carcinoma of the cervix
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera)
- Cardiac dysfunction as defined by:
- Myocardial infarction within the last 6 months of study entry, or
- Reduced left ventricular function with an ejection fraction < 50% as measured by MUG scan or echocardiogram or
- Unstable angina, or
- Unstable cardiac arrhythmias
- Hypersensitivity to the active substance or to any of the excipients of the drug product
- Pregnant or lactating females
- Unwilling or not capable to use effective means of birth control
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Part B:
- Severe cardiac dysfunction (NYHA classification II-IV, see appendix G)
- Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix F)
- Severe neurological or psychiatric disease
- Serious active infections
- Previous serious toxicities related to the use of lenalidomide
- CMV reactivation, which is not responsive to first line valganciclovir

Study & Design

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