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

• Conditions: Previously untreated acute myeloid leukemia (AML) or high riskmyelodysplastic syndrome (MDS); MedDRA version: 17.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 17.0Level: LLTClassification code 10028532Term: MyelodysplasiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-27
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 860

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
- 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, MRD evaluation and biobanking, 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, unless clearly disease related, 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 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 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 109/L
• Platelet count = 75 x 109/L
• Serum creatinine clearance = 30 ml/min
• 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 773
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 87

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
• 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