Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome
Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma
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 was planned as a phase I/II trial studying the side effects and determining the best dose of gemcitabine hydrochloride when given together with pemetrexed disodium. Unfortunately, due to a lack of funding, the phase II portion was never conducted.
Study Overview
Detailed Description
OBJECTIVES:
- 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)
OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride. Originally, this was designed to be followed by a phase II portion to determine the efficacy in this population. Unfortunately, due to a lack of funding, the phase II portion was never conducted.
During 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60611-3013
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Cohort 1
Pemetrexed at a dose of 400 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle. Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle. |
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of gemcitabine will be 800 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 1200 mg/m^2.
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of pemetrexed will be 400 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 500 mg/m^2.
|
|
Experimental: Cohort 2
Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle. Gemcitabine at a dose of 800 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle. |
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of gemcitabine will be 800 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 1200 mg/m^2.
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of pemetrexed will be 400 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 500 mg/m^2.
|
|
Experimental: Cohort 3
Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle. Gemcitabine at a dose of 1000 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle. |
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of gemcitabine will be 800 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 1200 mg/m^2.
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of pemetrexed will be 400 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 500 mg/m^2.
|
|
Experimental: Cohort 4
Pemetrexed at a dose of 500 mg/m2 will be given to patients on day 1 and day 15 of 28 day cycle. Gemcitabine at a dose of 1200 mg/m2 will be given following pemetrexed on day 1 and 15 of a 28-day cycle. |
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of gemcitabine will be 800 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 1200 mg/m^2.
Patients will be treated in cohorts of 3-6 per cohort.
The starting dose of pemetrexed will be 400 mg/m^2 given as an intravenous (IV) infusion on days 1 and 15 of each 28-day cycle.
The dose will be escalated for each subsequent cohort of patients, up to a maximum of 500 mg/m^2.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort.
Time Frame: From the day that the first treatment is given through the first 28 day period for each patient.
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Only dose limiting toxicities (DLT) were collected. DLTs were graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE The occurrence of any of the following toxicities during the first treatment cycle constitutes DLT in this study: Grade 3 and/or 4 non-hematologic toxicity other than grade 3 nausea or vomiting. Grade 3 and/or 4 unexpected non-hematologic toxicities. Grade 4 vomiting despite maximal antiemetic support. Grade 4 neutropenia and fever during first cycle. Grade 4 neutropenia on Day 1 of 2nd treatment cycle despite growth factor support or grade 4 thrombocytopenia on Day 1 of 2nd treatment cycle. |
From the day that the first treatment is given through the first 28 day period for each patient.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Barbara Pro, MD, Robert H. Lurie Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- stage I cutaneous T-cell non-Hodgkin lymphoma
- stage I mycosis fungoides/Sezary syndrome
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- stage II cutaneous T-cell non-Hodgkin lymphoma
- stage II mycosis fungoides/Sezary syndrome
Additional Relevant MeSH Terms
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Bacterial Infections and Mycoses
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, T-Cell
- Lymphoma
- Mycoses
- Mycosis Fungoides
- Sezary Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Folic Acid Antagonists
- Gemcitabine
- Pemetrexed
Other Study ID Numbers
- NU 05H8
- P30CA060553 (U.S. NIH Grant/Contract)
- STU00006771 (Other Identifier: Northwestern University IRB)
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