A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia
- Determine the safety and efficacy of fludarabine and thalidomide in patients with newly
diagnosed B-cell chronic lymphocytic leukemia.
- Determine the overall response rate (complete and partial) in patients treated with
- Determine the duration of response in patients treated with this regimen.
OUTLINE: This is an open-label, phase I, dose-escalation study of thalidomide followed by a
phase II study.
- Phase I: Beginning on day 1, patients receive oral thalidomide once daily for up to 6
months. Beginning on day 7, patients also receive fludarabine IV over 30 minutes daily
for 5 days. Treatment with fludarabine repeats every 28-35 days for up to 6 courses.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of thalidomide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive fludarabine and thalidomide as in phase I at the MTD.
Patients are followed at 4 weeks, every 3 months for 2 years, and then every 4 months for 2
PROJECTED ACCRUAL: Up to 45 patients (≥ 9 for the phase I portion and ≤ 36 for the phase II
portion) will be accrued for this study within 8 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Responders (Complete and Partial Response)
Criteria for response were based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response, which includes clinical, hematologic, and bone marrow features (Cheson, B.D., et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-97.)
4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Kelvin Lee, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|