Thalidomide With or Without Fludarabine in Treating Patients With Hematologic Cancer

Study Overview
=================
Brief Summary
-----------------
This randomized phase II trial is studying thalidomide and fludarabine to see how well they work compared to thalidomide alone in treating patients with hematologic cancer that has not responded to previous treatment with fludarabine. 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.

Detailed Description
-----------------
OBJECTIVES: I. Compare the safety and tolerability of thalidomide with or without fludarabine in patients with fludarabine-refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. II. 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.

Official Title
-----------------
Randomized Phase II Study of Thalidomide Versus Thalidomide Plus Fludarabine for Patients With Chronic Lymphocytic Leukemia Previously Treated With Fludarabine

Conditions
-----------------
Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Drug: fludarabine phosphate
* Drug: thalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Performance status - Karnofsky 60-100% At least 12 weeks See Disease Characteristics Bilirubin < 2.0 times upper limit of normal (ULN)* SGOT < 2.5 times ULN* Creatinine < 1.5 times ULN No history of cardiac arrhythmia No myocardial infarction within the past 6 months 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 At least 4 weeks since prior biologic therapy and recovered No concurrent growth factors (epoetin alfa, filgrastim [G-CSF], or sargramostim [GM-CSF]) 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 At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Recovered from any prior investigational agents No other concurrent investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (thalidomide)<br>Patients receive oral thalidomide once daily in the absence of disease progression or unacceptable toxicity. | Drug: thalidomide<br>* Given orally<br>* Other names: Thalomid;|
| Experimental: Arm II (thalidomide, fludarabine phosphate)<br>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. | Drug: fludarabine phosphate<br>* Given IV<br>* Other names: Fludara;Drug: thalidomide<br>* Given orally<br>* Other names: Thalomid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 |  | Up to 5 years | 
| Incidence of complete and partial remission |  | Up to 5 years |