RATIONALE: Thalidomide may stop the growth of hematologic cancer by stopping blood flow to the cancer. Combining thalidomide with fludarabine may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drug. It is not yet known whether thalidomide is more effective with or without fludarabine for hematologic cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of thalidomide with or without fludarabine in treating patients who have hematologic cancer that has not responded to previous treatment with fludarabine.

Condition	Treatment or Intervention	Phase
refractory chronic lymphocytic leukemia recurrent small lymphocytic lymphoma	Drug: fludarabine  Drug: thalidomide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy	Phase II

OBJECTIVES:

• Compare the safety and tolerability of thalidomide with or without fludarabine in patients with fludarabine-refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
• Compare the incidence of complete and partial remission in patients treated with these regimens.

OUTLINE: This is a randomized, open-label study. Patients are stratified according to time to relapse from last fludarabine treatment (less than 6 months vs more than 6 months). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral thalidomide once daily in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive thalidomide as in arm I and fludarabine IV over 30 minutes on days 1-5. Treatment with fludarabine repeats every 28 days for 6 courses. Once fludarabine is completed, patients continue to receive thalidomide alone as in arm I.

PROJECTED ACCRUAL: A total of 24-70 patients (12-35 per treatment arm) will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:
• Confirmed chronic lymphocytic leukemia (CLL), meeting the following criteria:
• Peripheral blood lymphocytosis greater than 5,000/mm^3
• Co-expression of the CD5, CD19, CD20, and CD23 surface antigens
• Clonal kappa and lambda light chain expression
• Dim surface immunoglobulin expression
• Small lymphocytic lymphoma
• Relapsed or refractory disease
• Must have received at least 1 prior regimen containing fludarabine
• Meets one of the following criteria:
• Recurrence of lymphocytosis greater than 5,000/mm^3 or an increase in lymph node volume greater than 50% after achieving complete (CR) or partial response (PR)
• Never achieved a CR or PR after receiving at least 2 courses of fludarabine IV for 5 days at a dose of 25 mg/m^2/day
• No other lymphoproliferative diseases or diseases due to transformation of CLL (e.g., prolymphocytic leukemia or Richter's syndrome)
• No known CNS disease

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 12 weeks

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin < 2.0 times upper limit of normal (ULN)*
• SGOT < 2.5 times ULN* NOTE: *Unless due to Gilbert's disease OR the result of CLL

Renal:

• Creatinine < 1.5 mg/dL

Cardiovascular:

• No history of cardiac arrhythmia
• No myocardial infarction within the past 6 months

Other:

• 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 pre-existing neurotoxicity grade 3 or greater
• No other medical condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Female patients must use 2 effective methods (at least 1 highly active method) of contraception 4 weeks before, during, and for 4 weeks after study participation and male patients must use effective barrier contraception during and for 4 weeks after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior biologic therapy and recovered
• No concurrent growth factors (epoetin alfa, filgrastim [G-CSF], or sargramostim [GM-CSF])

Chemotherapy:

• See Disease Characteristics
• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Recovered from any prior investigational agents
• No other concurrent investigational agents

New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting

Study chairs or principal investigators

Richard R. Furman, MD,  Study Chair,  Cornell University Medical College   

Study ID Numbers:  CDR0000068429; NYWCCC-MTS-00-0535ME; NCI-639
Record last reviewed:  April 2004
Record first received:  February 2, 2001
ClinicalTrials.gov Identifier:  NCT00009984
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18