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

Northwestern University

Status and phase: Terminated; Phase 1

Conditions: Lymphoma

Treatments: Drug: Pemetrexed; Drug: Gemcitabine

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00369629

P30CA060553 (U.S. NIH Grant/Contract)

STU00006771 (Other Identifier)

NU 05H8

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 4 patient groups

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Gemcitabine

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Gemcitabine

Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Gemcitabine

Cohort 4

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Gemcitabine