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

September 19, 2013 updated by: Roswell Park Cancer Institute

A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Responders (Complete and Partial Response)
Time Frame: 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.)
4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Duration of Response
Time Frame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
4 weeks, every 3 months for 2 years, and then every 4 months for 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Investigators

  • Principal Investigator: Kelvin Lee, MD, Roswell Park Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

November 9, 2004

First Submitted That Met QC Criteria

November 8, 2004

First Posted (Estimate)

November 9, 2004

Study Record Updates

Last Update Posted (Estimate)

October 24, 2013

Last Update Submitted That Met QC Criteria

September 19, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000391769
  • RPC-01-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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