Back to resultsGemcitabine and Bexarotene in Treating Patients With Progressive or Refractory Stage IB, Stage II, Stage III, or Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma (GemBex)
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
bexarotene
gemcitabine hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring 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
Eligibility 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
Sites / Locations
- Leeds Cancer Centre at St. James's University Hospital
- Saint Bartholomew's Hospital
- St. Thomas' Hospital
- Christie Hospital
- Southampton General Hospital
- Royal Cornwall Hospital
- Edinburgh Cancer Centre at Western General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GemBex
Arm Description
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.
Outcomes
Primary Outcome Measures
Rate of objective response
Secondary Outcome Measures
Duration and durability of objective disease response
Time from first date of treatment to the first date of diagnosis of progressive disease
Assessment of quality of life
Full Information
NCT ID
NCT00660231
First Posted
April 16, 2008
Last Updated
December 2, 2014
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT00660231
Brief Title
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
Acronym
GemBex
Official Title
A Phase II Study of Gemcitabine and Bexarotene (Gembex) in the Treatment of Cutaneous T-cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GemBex
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bexarotene
Other Intervention Name(s)
Targretin
Intervention Description
Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.
Primary Outcome Measure Information:
Title
Rate of objective response
Time Frame
at 24 weeks
Secondary Outcome Measure Information:
Title
Duration and durability of objective disease response
Description
Time from first date of treatment to the first date of diagnosis of progressive disease
Time Frame
up to 5 years after treatment start
Title
Assessment of quality of life
Time Frame
up to 5 years after treatment start
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim Illidge
Organizational Affiliation
The Christie NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leeds Cancer Centre at St. James's University Hospital
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Saint Bartholomew's Hospital
City
London
State/Province
England
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
St. Thomas' Hospital
City
London
State/Province
England
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro
State/Province
England
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Edinburgh Cancer Centre at Western General Hospital
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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