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

NCT ID: NCT00660231

Last Updated: 2014-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2014-01-31

Brief Summary

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

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

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GemBex

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.

Group Type: EXPERIMENTAL

bexarotene

Intervention Type: DRUG

Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.

gemcitabine hydrochloride

Intervention Type: DRUG

Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.

Interventions

bexarotene

Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.

Intervention Type: DRUG

gemcitabine hydrochloride

Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.

Intervention Type: DRUG

Other Intervention Names

Targretin

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Illidge

Role: PRINCIPAL_INVESTIGATOR

The Christie NHS Foundation Trust

Locations

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Saint Bartholomew's Hospital

London, England, United Kingdom

St. Thomas' Hospital

London, England, United Kingdom

Christie Hospital

Manchester, England, United Kingdom

Southampton General Hospital

Southampton, England, United Kingdom

Royal Cornwall Hospital

Truro, England, United Kingdom

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-UCL-GEMBEX

Identifier Type: -

Identifier Source: secondary_id

EU-20841

Identifier Type: -

Identifier Source: secondary_id

EUDRACT 2006-000591-33

Identifier Type: -

Identifier Source: secondary_id

UCL/06/009

Identifier Type: -

Identifier Source: org_study_id