Thalidomide With or Without Fludarabine in Treating Patients With Hematologic Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: fludarabine phosphate; Drug: thalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (thalidomide); Patients receive oral thalidomide once daily in the absence of disease progression or unacceptable toxicity.	Drug: thalidomide; Given orally; Other Names: Kevadon; Synovir; THAL; Thalomid
Experimental: Arm II (thalidomide, fludarabine phosphate); 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; Given IV; Other Names: 2-F-ara-AMP; Beneflur; Fludara; Drug: thalidomide; Given orally; Other Names: Kevadon; Synovir; THAL; Thalomid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Richard Furman, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 6, 2013
• Last Update Submitted That Met QC Criteria: June 5, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: NCI-2012-02393; N01CM62204 (U.S. NIH Grant/Contract); NYWCCC-MTS-00-0535ME; CDR0000068429; NCI-639