Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

This study has been completed.
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
First received: November 9, 2004
Last updated: September 19, 2013
Last verified: September 2013

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.

Condition Intervention Phase
Drug: fludarabine phosphate
Drug: thalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia

Resource links provided by NLM:

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Overall Responders (Complete and Partial Response) [ Time Frame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: May 2002
Study Completion Date: May 2012
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: fludarabine phosphate
Given IV
Drug: thalidomide

Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • At least 12 weeks


  • See Disease Characteristics


  • Bilirubin < 1.5 mg/dL
  • AST < 2.5 times upper limit of normal


  • Creatinine ≤ 1.5 mg/dL


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


  • 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


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • No prior therapy for CLL
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096018

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Principal Investigator: Kelvin Lee, MD Roswell Park Cancer Institute
  More Information

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00096018     History of Changes
Other Study ID Numbers: CDR0000391769  RPC-01-12 
Study First Received: November 9, 2004
Results First Received: January 28, 2013
Last Updated: September 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
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

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Fludarabine phosphate
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016