Gemcitabine and Bexarotene in Treating Patients With Progressive or Refractory Stage IB, Stage II, Stage III, or Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and bexarotene, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying giving gemcitabine together with bexarotene to see how well it works in treating patients with progressive or refractory stage IB, stage II, stage III, or stage IV cutaneous T-cell non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Primary Confirm the feasibility and efficacy of the combination of gemcitabine hydrochloride and bexarotene in patients with cutaneous T-cell lymphoma whose disease is no longer controlled by skin-directed therapy and who have had at least one prior systemic therapy. Secondary Determine the rate of objective disease control as defined by complete response (CR), clinical complete response (CCR), partial response (PR), and stable disease (SD) for 6 months as determined by the Objective Primary Disease Response Evaluation Criteria (OPDREC). Evaluate the duration and durability of objective disease response (CR, CCR and PR) as determined by OPDREC criteria. Evaluate time to objective disease response. Determine the safety of this combination in terms of adverse events, clinical laboratory data, physical examinations, rate of neutropenic fever and sepsis, blood transfusions, and treatment compliance. Determine the time to objective disease progression. Determine the time to treatment failure. Determine change from baseline in Severity-Weighted Assessment Tool (SWAT) value, Erythroderma SWAT value, Pruritus Visual Analogue Scale, and ECOG performance status. Determine proportion of disease control, response, and progression as determined by RECIST criteria. Evaluate the proportion of patients with clearing of Sézary cells from the blood and bone marrow. Measure changes in patient assessed Quality of Life using Skindex 29 and EORTC QLQ-30. OUTLINE: This is a multicenter study. Patients receive gemcitabine hydrochloride IV on days 1 and 8 and oral bexarotene daily on days 1-21. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses of study therapy, patients with responding disease receive oral bexarotene alone daily until disease progression or treatment no longer tolerated. Patients complete a quality of life questionnaire at baseline, during study therapy, and after completion of study treatment. After completion of study treatment, patients are followed every 2 months for up to 5 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK

Official Title
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A Phase II Study of Gemcitabine and Bexarotene (Gembex) in the Treatment of Cutaneous T-cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bexarotene
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cutaneous T-cell lymphoma (CTCL) including its variants (e.g., mycosis fungoides and Sézary syndrome) CTCL stage IB, IIA, IIB, III or IVA disease No visceral involvement (i.e., stage IVB disease) Lymphadenopathy is allowed Patients must have developed progressive disease after receiving or have been refractory to at least 1 course of prior standard, systemic, skin-directed therapy (e.g., interferon, chemotherapy, or denileukin diftitox [Ontak®]) No CD30 + (Ki1+ve) anaplastic large cell lymphoma PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 6 months Hemoglobin ≥ 9.0 g/dL (transfusions and/or erythropoietin are allowed) ANC > 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Total bilirubin ≤ 1.25 times upper limit of normal (ULN) AST and ALT ≤ 2 times ULN Serum creatinine ≤ 2 times ULN No clinically significant active infection No uncontrolled diabetes mellitus No excessive alcohol consumption No biliary tract disease No history of pancreatitis HIV negative Hepatitis B and C negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study participation No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer, cervical epithelial neoplasm CIN1, or carcinoma in situ No other significant medical or psychiatric condition that would preclude study compliance PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 4 weeks since any prior investigational agent More than 2 weeks since prior topical steroids or more than 4 weeks since prior systemic steroids Local radiotherapy may be given to isolated symptomatic tumour nodules that require immediate treatment for up to 2 weeks prior to study drugs No prior treatment with bexarotene (Targretin®) No concurrent anticancer therapy No concurrent investigational agent No concurrent drug therapy with other medications that can elevate triglycerides or cause pancreatic toxicity (e.g., gemfibrozil) No concurrent warfarin

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GemBex<br>Gemcitabine days 1 and 8 of a 3 week cycle (4 cycles total - 12 weeks) Bexarotene daily: in combination with Gemcitabine during first 12 weeks, then Bexarotene maintenance until disease progression. | Drug: bexarotene<br>* Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.<br>* Other names: Targretin;Drug: gemcitabine hydrochloride<br>* Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of objective response |  | at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration and durability of objective disease response | Time from first date of treatment to the first date of diagnosis of progressive disease | up to 5 years after treatment start | 
| Assessment of quality of life |  | up to 5 years after treatment start | 

 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 IB mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage IB cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma