Lenalidomide in Patients With Chronic Myelomonocytic Leukemia

Study Overview
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Brief Summary
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In a phase I study the investigators plan to investigate safety and toxicity of lenalidomide in patients with Chronic Myelomonocytic Leukemia (CMML). A phase II study will be started once an optimal dose has been found. The primary endpoint will concern the efficacy of lenalidomide in patients with CMML according to the WHO diagnostic criteria.

Official Title
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A Phase I/II Study of Lenalidomide in Patients With Chronic Myelomonocytic Leukemia

Conditions
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Chronic Myelomonocytic Leukemia

Intervention / Treatment
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* Drug: Revlimid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CMML according to the WHO diagnostic criteria. Understand and voluntarily sign an informed consent form. Age >=18 years at the time of signing the informed consent form. Able to adhere to the study visit schedule and other protocol requirements. All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study. Patients carrying a somatic mutation involving the platelet derived growth factor receptor beta (PDGFRB) can be included if standard treatment with imatinib failed. ECOG performance status of <= 2 at study entry. Laboratory test results within these ranges: Creatinine clearance > 30ml/min AST (SGOT) and ALT (SGPT) <= 2.5 x ULN Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Female subjects of childbearing potential must: Understand the study drug is expected to have a teratogenic risk Agree to use two effective contraception Male subjects must Agree to use condoms Agree not to donate semen All subjects must Agree to abstain from donating blood Agree not to share study drug with another person Exclusion Criteria: Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. Use of any other experimental drug or therapy within 28 days of baseline. Known hypersensitivity to thalidomide. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. Any prior use of lenalidomide. Concurrent use of other anti-cancer agents or treatments. Known positive for HIV or infectious hepatitis, type A, B or C.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Revlimid|Dose escalation 5mg - 10mg - 15mg - 20mg in cohorts of three patients The first step of phase I will be 5 mg lenalidomide in a daily regimen, the next step will be 10 mg in a daily regimen, the dosis of the following steps will be increased by 5 mg each until dose limiting toxicity (DLT) is reached. Phase II will be started at the MTD (1 dose step below DLT) and will be administered in a daily regimen.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | This is a phase I/II, open-label, dose-escalation study of lenalidomide in patients with CMML. In phase I of the study the primary purpose is to determine the MTD. The purpose of phase II is to determine the response rate. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and seriousness of adverse events to evaluate safety and tolerability | For both phases (phase I and II), secondary objectives are to evaluate safety, tolerability, efficacy and analysis of molecular markers. | 4 years | 
| Number of patients achieving transfusion independence | Phase II | 4 years | 
| Progression free survival, Overall survival | Phase II | 4 years | 
| Patients achieving cytogenetic response | Phase II; Cytogenetic response assessment requires 20 analyzable metaphases using conventional cytogenetic techniques, FISH may be used an a supplement to follow a specifically defined cytogenetic abnormality | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMML, Chronic myelomonocytic leukemia, Lenalidomide, Revlimid