A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia
18 Years
N/A
Both
Leukemia
Trial Information
A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia
OBJECTIVES:
- 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
this regimen.
- 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
years.
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) based on the
following criteria:
- Peripheral blood lymphocytosis > 5,000/mm^3
- Co-expression of CD5, CD19 or CD20, and CD23 surface antigens
- Clonal kappa or lambda light chain expression
- No recurrent or refractory CLL
- No other lymphoproliferative diseases or diseases due to transformation of CLL, such
as prolymphocytic leukemia or Richter's syndrome
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- At least 12 weeks
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin < 1.5 mg/dL
- AST < 2.5 times upper limit of normal
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- No cardiac arrhythmia within the past 6 months
- No myocardial infarction within the past 6 months
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use at least 1 highly active and 1 additional method of
contraception for 4 weeks before, during, and for at least 4 weeks after study
treatment
- Patients must have sufficient mental capacity to understand the study explanation and
provide informed consent
- No other malignancy within the past 5 years except basal cell skin cancer or
carcinoma in situ of the cervix
- No active serious infection uncontrolled by antibiotics
- No medical condition or reason that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No prior therapy for CLL
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall Responders (Complete and Partial Response)
Outcome Description:
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.)
Outcome Time Frame:
4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Safety Issue:
No
Principal Investigator
Kelvin Lee, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000391769
NCT ID:
NCT00096018
Start Date:
May 2002
Completion Date:
May 2012
Related Keywords:
- Leukemia
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- B-cell chronic lymphocytic leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
