A phase II study of Gemcitabine and Bexarotene (GemBex) in the treatment of cutaneous T-cell lymphoma

ISRCTN ISRCTN18563749
DOI https://doi.org/10.1186/ISRCTN18563749
ClinicalTrials.gov (NCT) NCT00660231
Clinical Trials Information System (CTIS) 2006-000591-33
Protocol serial number 1756
Sponsor University College London (UCL) (UK)
Funder Cancer Research UK (CRUK) (UK) (ref: C431/A6857)
Submission date
31/03/2010
Registration date
31/03/2010
Last edited
26/10/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-gemcitabine-and-bexarotene-for-people-with-t-cell-lymphoma-of-the-skin

Contact information

Ms Bilyana Popova
Scientific

Cancer Research UK & UCL Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Study information

Primary study designInterventional
Study designNon-randomised multicentre interventional and observational treatment validation of investigation/therapeutic process
Secondary study designNon randomised study
Study type Participant information sheet
Scientific titleA phase II, multicentre, non-randomised, open-label, single arm trial of the efficacy of Gemcitabine and Bexarotene in patients who have developed progressive cutaneous T-cell lymphoma (CTCL)
Study acronymGemBex
Study objectivesThis is a phase II, multicentre, non-randomised, open-label, single arm trial of Gemcitabine and Bexarotene for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have developed progressive disease after receiving, or have been refractory to, standard skin-directed therapy and at least one prior systemic therapy. The study aims to to evaluate the efficacy of Gemcitabine and Bexarotene as a combination therapy in patients with CTCL in terms of the rate of objective disease response and its duration, and to determine whether the combination has sufficient biological activity in CTCL to warrant more extensive investigation. This is a "two stage" study where 35 patients will be treated initially and if the response criteria are met, further 49 to a total of 84 patients will be treated on the study.
Ethics approval(s)Leeds (East) Research Ethics Committee, 10/05/2006, ref: 06/Q1206/65
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Lymphoma; Disease: Lymphoma (non-Hodgkin's)
InterventionProphylactic fenofibrate; patients start prophylactic Fenofibrate 160 - 200 mg daily 7 days before chemotherapy. Initial chemotherapy: 4 x 21 day cycles:
Gemcitabine 1000 mg/m^2 intravenous (iv) days 1 and 8
Bexarotene 300 mg/m^2 orally (po) daily*
* Bexarotene given at a reduced dose of 150 mg/m^2 for weeks 1 and 2 of cycle 1 and, if tolerated, increased to 300 mg/m^2 as per British Dermatology Society guidelines

In patients responding after 4 cycles of Gemcitabine + Bexarotene:
Bexarotene maintenance 300 mg/m^2 daily until disease progression or patient

Study Entry: Registration only
Details: As this is a single arm study, all patients registered will recieve the same treatment.
Intervention typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Gemcitabine and Bexarotene (GemBex), Fenofibrate
Primary outcome measure(s)

To confirm the feasibility and efficacy of the combination of Gemcitabine and Bexarotene in patients, assessed during time from treatment start to progression

Key secondary outcome measure(s)

Assessed during time from treatment start to progression:
1. To evaluate the rate of objective disease control
2. To evaluate the duration and durability

Completion date31/07/2012

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration84
Key inclusion criteria1. Males or non-pregnant females aged greater than 18 years
2. Histologically confirmed diagnosis of cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sézary syndrome
3. Stage Ib, IIa, IIb, III, IVa and IVb disease
4. Patients who have failed standard skin-directed therapy and have had at least 1 course of prior systemic therapy, such as interferon, chemotherapy, Denileukin diftitox (Ontak®) which they have either failed to respond to or have subsequently progressed
5. Anticipated life expectancy greater than six months
6. Written informed consent to participate in the study. vii.Bexarotene naive or previous response to single-agent bexarotene, but more than 3 months since last treatment with bexarotene
Key exclusion criteria1. Eastern Cooperative Oncology Group (ECOG) Performance Status greater than 1
2. Patients who have not received at least 1 course of prior systemic therapy for CTCL
3. CD30 + (Ki1+ve) anaplastic large cell lymphoma
4. Patients who have failed previous treatment with Bexarotene (Targretin®)
5. Patients who have previously experienced a severe adverse reaction to Bexarotene
6. Concomitant use of any anti-cancer therapy
7. Concomitant use of any investigational agent
8. Use of any investigational agent within 4 weeks of study entry
9. Clinically significant active infection
10. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
11. Excessive alcohol consumption
12. Uncontrolled diabetes mellitus
13. Biliary tract disease
14. History of pancreatitis
15. Concomitant drug therapy with other medications that can elevate triglycerides or cause pancreatic toxicity e.g. Gemfibrozil
16. Inadequate bone marrow or other organ function, as evidenced by: Unsupported haemoglobin less than 9.0 g/dL (transfusions and/or erythropoietin are permitted); Absolute neutrophil count (ANC) = 1.5 x 10^9/L; Platelet count less than 100 x 10^9/L
17. Total bilirubin greater than 1.25 x upper limit of normal (ULN) for institution, aspartate transaminase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/glutamic pyruvic transaminase (ALT/SGPT) greater than 2.0 x ULN, serum creatinine greater than 2 x ULN for age and sex
18. Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin or cervical epithelial neoplasm [CIN1, carcinoma in situ] that has been treated curatively)
19. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures
20. Patients who are pregnant or breast-feeding (all women of child bearing potential must use the contraceptive pill or intrauterine contraceptive device (IUCD) during the treatment period and for at least 1 month thereafter). Male patients must use a barrier method of contraception during the treatment period and for at least 1 month thereafter.
21. Any treatment for lymphoma, including photopheresis, within the 4 weeks prior to entering the study. For patients receiving long-term corticosteroid therapy, the dose should ideally be stopped and if this is not feasible reduced to as low as possible. If steroids cannot be stopped, patients who have been on stable doses less than or equal to 20 mg for at least 3 months can be entered into the study. Local radiotherapy to isolated symptomatic tumour nodules requiring immediate treatment may be given until 2 weeks prior to entering the study.
22. Warfarin
Date of first enrolment29/07/2008
Date of final enrolment31/07/2012

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Cancer Research UK & UCL Trials Centre
London
W1T 4TJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 12/11/2013 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Plain English results No Yes
Study website Study website 11/11/2025 11/11/2025 No Yes

Editorial Notes

26/10/2018: Cancer Research UK lay results summary link added to Results (plain English)

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