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

Lymphoma Clinical Trial

Official title:

Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00369629
• Other study ID #: NU 05H8
• Secondary ID: P30CA060553STU00
• Status: Terminated
• Phase: Phase 1
• Start date: August 28, 2006
• Est. completion date: June 4, 2013

Study information

• Verified date: August 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: June 4, 2013
• Est. primary completion date: July 16, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Mycoses
• Mycosis Fungoides
• Sezary Syndrome

Intervention

Drug:
• Gemcitabine
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.
• Pemetrexed
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.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	Eli Lilly and Company, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the day that the first treatment is given through the first 28 day period for each patient.