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

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

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