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

Phase 1TerminatedNCT00369629

Northwestern University14 enrolled

Overview

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.

OBJECTIVES: 1. Determine the safety and tolerability of gemcitabine hydrochloride and pemetrexed disodium in patients with advanced mycosis fungoides or Sézary syndrome. (Phase I) 2. 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

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

GemcitabineDRUG

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.

PemetrexedDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Maximum Tolerated Dose as Measured by the Number of Dose Limiting Toxicities Seen in Cohort.

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.

Time frame: From the day that the first treatment is given through the first 28 day period for each patient.