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Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Timothy Kuzel, Northwestern University
ClinicalTrials.gov Identifier:
NCT00369629
First received: August 24, 2006
Last updated: March 20, 2013
Last verified: March 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with pemetrexed disodium may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gemcitabine hydrochloride when given together with pemetrexed disodium and to see how well they work in treating patients with advanced mycosis fungoides or Sézary syndrome.


Condition Intervention Phase
Lymphoma
 Drug: gemcitabine hydrochloride
Drug: pemetrexed disodium
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Primary Phase I [ Time Frame: Every 2 weeks of 28 day cycle ] [ Designated as safety issue: Yes ]
    To determine safety and tolerability associated with gemcitabine, administered via the dose-rate schedule every 2 weeks, and pemetrexed, administered every 2 weeks of a 28 day cycle, as combination therapy in patients with advanced stage mycosis fungoides/Sézary syndrome based on adverse events such as clinical and laboratory findings.

  • Primary Phase II [ Time Frame: As needed ] [ Designated as safety issue: Yes ]
    To evaluate tumor response in this patient population according to the Composite Assessment (CA) of Index Lesion Disease Severity with measurement of both cutaneous and extra-cutaneous manifestations of disease. To evaluate synergistic toxic effects associated with gemcitabine/pemetrexed therapy.


Estimated Enrollment: 38
Study Start Date: June 2006
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine and Pemetrexed Disodium Drug: gemcitabine hydrochloride
Gemcitabine has shown clinical activity in patients with advanced CTCL with a low toxicity profile 15, 16. It was investigated at 2 centers in a phase II trial at a dosage of 1200 mg/m2 (using traditional 3-weekly dosing every 28 days over 30 minutes) in 44 patients with clinical stage IIB-IV MF/SS 15. Twelve percent of patients achieved CR and 26% of patients achieved PR, with a median duration of 15 months and 10 months, respectively. Gemcitabine at a similar dose schedule was also evaluated in 32 patients with untreated MF, peripheral T-cell lymphoma, unclassified (PTCLU), and SS 16. The overall response rate was 75% with CR in 22% and PR in 53% of patients. The reported median duration was 10 months.
Drug: pemetrexed disodium
This agent has shown activity in a wide variety of solid tumors, including non-small cell lung, mesothelioma, breast, bladder, head and neck, and colon cancers 19, 20. Preclinical studies have shown cytotoxic synergy in various tumor cells when pemetrexed was combined with gemcitabine 21, 22. This provided a rationale for studying the drugs in combination. Phase I studies have shown antitumor activity in pre-treated and advanced solid tumors without increased toxicity 23-25. No pharmacokinetic interaction between the 2 drugs was observed. Clinical benefit response as well as survival data suggest a possible advantage over conventional gemcitabine monotherapy.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and tolerability of gemcitabine hydrochloride and pemetrexed disodium in patients with advanced mycosis fungoides or Sézary syndrome. (Phase I)
  • Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with pemetrexed disodium in these patients. (Phase I)
  • Evaluate tumor response (cutaneous and extracutaneous manifestations) in patients treated with this regimen. (Phase II)
  • Evaluate synergistic toxic effects associated with this treatment regimen in these patients. (Phase II)

Secondary

  • Assess response duration in patients treated with this regimen. (Phase II)
  • Assess time to response in patients treated with this regimen. (Phase II)
  • Assess time to progression in patients treated with this regimen. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride followed by a phase II study.

  • Phase I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≥ 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is defined as the dose one level below the MTD.

  • Phase II: Patients receive pemetrexed disodium and gemcitabine hydrochloride at the recommended phase II dose as in phase I. Treatment continues for ≥ 2 courses in the absence of unacceptable toxicity or disease progression or for 2 courses past maximum response.

After completion of study treatment, patients are followed every 3 months for up to 1 year.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* mycosis fungoides or Sézary syndrome

    • Stage IB-IVB disease NOTE: *Pathology report must read diagnostic or consistent with mycosis fungoides/Sézary syndrome
  • Failed ≥ 1 prior systemic treatment

  • Measurable disease

    • At least 1 indicator lesion must be designated prior to study entry

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 6 months
  • Creatinine ≤ 2.0 mg/dL
  • Creatinine clearance ≥ 45 mL/min
  • Bilirubin ≤ 2.2 mg/dL
  • AST and ALT ≤ 2 times upper limit of normal
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • No acute infection requiring systemic treatment
  • No history of severe hypersensitivity reaction to the study drugs or to any other ingredient used in their formulation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior topical therapy, systemic chemotherapy, or biological therapy
  • No acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 days before and for 2 days after pemetrexed disodium infusion (5 days before and for 2 days after pemetrexed disodium infusion for patients taking NSAIDs with a long half-life [e.g., naproxen, refocoxib, or celecoxib])
  • No concurrent topical agents except emollients
  • No other concurrent topical or systemic anticancer therapies
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369629

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Timothy M. Kuzel, MD Robert H. Lurie Cancer Center
Study Chair: Christiane Querfeld, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Timothy Kuzel, Timothy Kuzel, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00369629     History of Changes
Other Study ID Numbers: NU 05H8, P30CA060553
Study First Received: August 24, 2006
Last Updated: March 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
recurrent mycosis fungoides/Sezary syndrome
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
 stage I 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
recurrent cutaneous T-cell non-Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Gemcitabine
Pemetrexed
 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
Folic Acid Antagonists

ClinicalTrials.gov processed this record on May 19, 2013