GemBex: 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

Sponsor

University College, London (Other)

Overall Status

Completed

CT.gov ID

NCT00660231

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: bexarotene Drug: gemcitabine hydrochloride	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: bexarotene Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated. Other Names: Targretin Drug: gemcitabine hydrochloride Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.

Arm

Intervention/Treatment

Experimental: 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.

Drug: bexarotene

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

Other Names:

Targretin

Drug: gemcitabine hydrochloride

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

Outcome Measures

Primary Outcome Measures

Rate of objective response [at 24 weeks]

Secondary Outcome Measures

Duration and durability of objective disease response [up to 5 years after treatment start]
Time from first date of treatment to the first date of diagnosis of progressive disease
Assessment of quality of life [up to 5 years after treatment start]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
2	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
3	St. Thomas' Hospital	London	England	United Kingdom	SE1 7EH
4	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
5	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
6	Royal Cornwall Hospital	Truro	England	United Kingdom	TR1 3LJ
7	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU