Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome

Study Overview
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Brief Summary
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RATIONALE: Lenalidomide may stop the growth of mycosis fungoides/Sezary syndrome by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well lenalidomide works in treating patients with relapsed mycosis fungoides/Sezary syndrome.

Detailed Description
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OBJECTIVES: Primary Determine the response rate and duration of response in patients with relapsed mycosis fungoides/Sézary syndrome treated with lenalidomide. Determine the progression-free survival of patients treated with this drug. Secondary Determine the toxicity of this drug in these patients. Correlate the antiangiogenetic and costimulatory effects of this drug with clinical activity in skin biopsies from these patients. Assess the specific immune effector cell recruitment and augmentation of antitumor response in these patients. (Northwestern University only) OUTLINE: This is a multicenter study. Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 2 courses. Patients with progressive disease are removed from study. Patients achieving complete response receive 2 additional courses of treatment beyond complete response. Patients achieving partial response or stable disease may continue to receive lenalidomide as above for up to 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo tissue biopsies at baseline and on day 1 of course 2. Tissue specimens are analyzed for vessel density, presence of adhesion molecules, and immunophenotyping of dermal infiltrate.* NOTE: *At Northwestern University only, blood and tissue samples from 5-10 patients are collected. Peripheral blood samples are analyzed for immune cell repertoire (CD4+, CD8+ T cells, NK cells, NKT cells, CD4+, CD25+ T-regulatory cells, monocytes, and dendritic cell subsets), cell surface molecules, and for TH1/TH2-associated cytokines, such as interleukin (IL)-2, IL-4, IL-10, IL-12, interferon gamma, and tumor necrosis factor alpha, by flow cytometry at baseline, day 15 of course 1, and at the end of course 1. Immunological activation is assessed by analyzing surface expression of CD45RO and CTLA-4 on CD4+ and CD8+ T cells in blood and skin samples. Skin specimens are stored for future research studies on predictive markers of lenalidomide activity. After completion of study treatment, patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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Phase II Trial of CC-5013 (Lenalidomide, Revlimid®) in Patients With Cutaneous T-Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed mycosis fungoides/Sézary syndrome Stage IA-IVB disease Must have failed ≥ 1 prior topical treatment, including any of the following: Steroids Nitrogen mustard Retinoids Phototherapy Photochemotherapy Radiotherapy Total skin electron beam Measurable disease with ≥ 1 indicator lesion designated prior to study entry Erythrodermic patients are eligible PATIENT CHARACTERISTICS: ECOG performance status 0-2 WBC ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 2.0 mg/dL Bilirubin ≤ 2.2 mg/dL AST and ALT ≤ 2 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile women must use effective double-method contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy Fertile men must use effective contraception during and for ≥ 4 weeks after completion of study therapy No other malignancy within the past 5 years except treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, or surgically removed melanoma in situ of the skin (stage 0), with histologically confirmed free margins of excision and no current evidence of disease No acute infection requiring systemic treatment No known allergic reaction or hypersensitivity to thalidomide PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 4 weeks since prior topical therapy, systemic chemotherapy, or biological therapy No prior stem cell transplantation No other concurrent systemic antipsoriatic or anticancer therapies, including radiotherapy, thalidomide, or other investigational agents No other concurrent topical agents except emollients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br> | Drug: lenalidomide<br>* 10 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, increasing dose by 5 mg every cycle, up to a maximum of 25 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Treatment | In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following: CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal. PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required. | After cycle 4 of treatment (1 cycle =28 days) | 
| Progression-free Survival (PFS) | PFS is defined from the time of treatment initiation until documentation of progressive disease or death from any cause. Progressive disease is defined as (PD) ≥25% increase in CA ratio, ≥25% increase in no. or area of clinically abnormal lymph nodes/new tumors/new pathologically positive lymph nodes/visceral disease/an increase >25% in no. of Sézary cells. | From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years) | 
| Duration of Response (DOR) | DOR is defined as time of initial documentation of response to the time of documentation of progression in patients who achieve either a complete response (CR) and partial response (PR) | From time of initial response until progressive disease (up to approximately 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 | Toxicity is defined as the number of patients who patients who experienced an adverse event that was determined to be at least possibly related to study drug and determined to be a grade 3 or higher in severity as assessed by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where generally: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE | From treatment initiation until up to 30 days post treatment with possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of treatment permitted if meeting response criteria | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent mycosis fungoides/Sezary syndrome, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome