Clinical trial NCT00096018: Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
Official title: A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: 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
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2004-11-09
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Responders (Complete and Partial Response)
timeFrame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
measure: Duration of Response
timeFrame: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Kelvin Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chanan-Khan A, Miller KC, Takeshita K, Koryzna A, Donohue K, Bernstein ZP, Mohr A, Klippenstein D, Wallace P, Zeldis JB, Berger C, Czuczman MS. Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood. 2005 Nov 15;106(10):3348-52. doi: 10.1182/blood-2005-02-0669. Epub 2005 Jul 28.