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)

Phase 1

• Conditions: previously untreated acute myeloid leukemia (AML) or high risk myelodysplasie (MDS); MedDRA version: 19.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 19.0Level: LLTClassification code 10028532Term: MyelodysplasiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-12
• Last Update Posted: 17 May 2016

Recruitment & Eligibility

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

Inclusion Criteria

•Age 18-65 years, inclusive
•Patients with
oa 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
oacute leukemia’s of ambiguous lineage according to WHO 2008 or
oa 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 at diagnosis 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:
oSerum 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.
oSerum bilirubin =2.5 x upper limit of normal (ULN)
oAspartate transaminase (AST) = 2.5 x ULN
oAlanine transaminase (ALT) = 2.5 x ULN
oAlkaline 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 109/L
•Platelet count = 75 x 109/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:
obasal and squamous cell carcinoma of the skin
oin 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:
oMyocardial infarction within the last 6 months of study entry, or
oReduced left ventricular function with an ejection fraction < 50% as measured by MUG scan or echocardiogram or
oUnstable angina, or
oUnstable 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