Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma
18 Years
N/A
Both
Lymphoma
Trial Information
Phase I/II Trial of Gemcitabine/Pemetrexed Combination in Patients With Advanced Cutaneous T-Cell Lymphoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Primary Phase I
Outcome Description:
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.
Outcome Time Frame:
Every 2 weeks of 28 day cycle
Safety Issue:
Yes
Principal Investigator
Timothy M. Kuzel, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NU 05H8
NCT ID:
NCT00369629
Start Date:
June 2006
Completion Date:
September 2014
Related Keywords:
- Lymphoma
- 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
- Lymphoma
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, T-Cell, Cutaneous
Name | Location |
|---|---|
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
