Leukemia
Conditions
Keywords
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
Brief summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies such as thalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Combining fludarabine with thalidomide may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of thalidomide when given together with fludarabine and to see how well they work in treating patients with newly diagnosed B-cell chronic lymphocytic leukemia.
Detailed description
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.
Interventions
DRUGfludarabine phosphate
Given IV
DRUGthalidomide
Orally
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Responders (Complete and Partial Response) | 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years | 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.) |
| Duration of Response | 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years | — |
Countries
United States
Participant flow
Recruitment details
Study Activated: 3/21/2002. Study Closed: 11/19/2010
Participants by arm
| Arm | Count |
|---|---|
| Phase I - Dose Escalation Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days) | 13 |
| Phase II Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days) | 25 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Became Ineligible (not treated) | 0 | 3 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Miscellaneous | 2 | 1 |
| Overall Study | Miscellaneous (not treated) | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Phase I - Dose Escalation | Phase II | Total |
|---|---|---|---|
| Age, Customized 30 - 39 years | 2 participants | 0 participants | 2 participants |
| Age, Customized 40 - 49 years | 1 participants | 2 participants | 3 participants |
| Age, Customized 50 - 59 years | 2 participants | 8 participants | 10 participants |
| Age, Customized 60 - 69 years | 5 participants | 9 participants | 14 participants |
| Age, Customized 70 - 79 years | 3 participants | 6 participants | 9 participants |
| Region of Enrollment United States | 13 participants | 25 participants | 38 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 9 Participants | 18 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 13 | 25 / 25 |
| serious Total, serious adverse events | 6 / 13 | 15 / 25 |
Outcome results
Primary
Duration of Response
Time frame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Population: Patients with Complete or Partial Response
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I - Dose Escalation | Duration of Response | 43.3 months | Standard Deviation 11.3 |
| Phase II | Duration of Response | 30.0 months | Standard Deviation 16.4 |
Primary
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.)
Time frame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Population: All Treated Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I - Dose Escalation | Overall Responders (Complete and Partial Response) | 8 participants |
| Phase II | Overall Responders (Complete and Partial Response) | 18 participants |