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 (GemBex)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT00660231
First received: April 16, 2008
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Lymphoma
Drug: bexarotene
Drug: gemcitabine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine and Bexarotene (Gembex) in the Treatment of Cutaneous T-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Rate of objective response [ Time Frame: at 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration and durability of objective disease response [ Time Frame: up to 5 years after treatment start ] [ Designated as safety issue: No ]
    Time from first date of treatment to the first date of diagnosis of progressive disease

  • Assessment of quality of life [ Time Frame: up to 5 years after treatment start ] [ Designated as safety issue: No ]

Estimated Enrollment: 84
Study Start Date: March 2008
Estimated Study Completion Date: September 2016
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Targretin
Drug: gemcitabine hydrochloride
Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660231

Locations
United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
St. Thomas' Hospital
London, England, United Kingdom, SE1 7EH
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Cornwall Hospital
Truro, England, United Kingdom, TR1 3LJ
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Tim Illidge Christie Hospital NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00660231     History of Changes
Other Study ID Numbers: UCL/06/009, CRUK-UCL-GEMBEX, EU-20841, EUDRACT 2006-000591-33
Study First Received: April 16, 2008
Last Updated: March 26, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Authority

Keywords provided by University College, London:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Bexarotene
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Anticarcinogenic Agents
Protective Agents

ClinicalTrials.gov processed this record on July 10, 2014