Chemotherapy in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00003829

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

110

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Alternating treatment with more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine alternating with cyclophosphamide in treating patients who have previously untreated chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cyclophosphamide Drug: fludarabine phosphate	Phase 2

Detailed Description

OBJECTIVES: I. Determine the rate and duration of complete and partial remissions in patients with previously untreated B-cell chronic lymphocytic leukemia after treatment with alternating courses of fludarabine and cyclophosphamide. II. Monitor and assess toxicity of this regimen in these patients. III. Utilize molecular genetic studies and flow cytometry on peripheral blood cells from patients achieving complete remission by conventional criteria.

Apply FISH techniques using probes to chromosomes 12 and 13 as prognostic factors for time to progression and overall survival of these patients.

OUTLINE: Patients receive alternating courses of fludarabine and cyclophosphamide. Fludarabine is administered IV over 10-30 minutes on days 1-5 of courses 1, 3, and 5. Cyclophosphamide is administered IV over 30-60 minutes on day 1 of courses 2, 4, and 6. Treatment repeats every 4 weeks. Patients achieving clinical complete remission (CCR) after 6 courses of chemotherapy receive 2 additional courses (one course of each drug). Patients achieving partial remission after 6 courses of chemotherapy also receive 2 additional courses. If these patients then achieve CCR, they receive another 2 courses. Patients are followed every 3 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Alternating Cycles of Fludarabine and Cyclophosphamide in Previously Untreated Patients With B-cell CLL

Study Start Date :

Aug 1, 1999

Actual Primary Completion Date :

May 1, 2001

Actual Study Completion Date :

Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: fludarabine + cyclophosphamide Patients receive alternating courses of fludarabine and cyclophosphamide. Fludarabine is administered IV over 10-30 minutes on days 1-5 of courses 1, 3, and 5. Cyclophosphamide is administered IV over 30-60 minutes on day 1 of courses 2, 4, and 6. Treatment repeats every 4 weeks. Patients achieving clinical complete remission (CCR) after 6 courses of chemotherapy receive 2 additional courses (one course of each drug). Patients achieving partial remission after 6 courses of chemotherapy also receive 2 additional courses. If these patients then achieve CCR, they receive another 2 courses. Patients are followed every 3 months.	Drug: cyclophosphamide Drug: fludarabine phosphate

Arm

Intervention/Treatment

Experimental: fludarabine + cyclophosphamide

Patients receive alternating courses of fludarabine and cyclophosphamide. Fludarabine is administered IV over 10-30 minutes on days 1-5 of courses 1, 3, and 5. Cyclophosphamide is administered IV over 30-60 minutes on day 1 of courses 2, 4, and 6. Treatment repeats every 4 weeks. Patients achieving clinical complete remission (CCR) after 6 courses of chemotherapy receive 2 additional courses (one course of each drug). Patients achieving partial remission after 6 courses of chemotherapy also receive 2 additional courses. If these patients then achieve CCR, they receive another 2 courses. Patients are followed every 3 months.

Drug: cyclophosphamide

Drug: fludarabine phosphate

Outcome Measures

Primary Outcome Measures

proportion of confirmed responses [Up to 6 months]

Secondary Outcome Measures

overall survival [Up to 5 years]
progression free survival [Up to 5 years]
time to progression [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (CLL) manifested by all of the following: Threshold peripheral lymphocyte count greater than 5000/mm3 Small to moderate peripheral lymphocytes with no greater than 55% prolymphocytes Peripheral lymphocyte count less than 15,000/mm3 At least 30% lymphoid cells in bone marrow

Monoclonality of B lymphocytes Active disease by at least one of the following criteria:

Weight loss of at least 10% within the past 6 months or prolonged fever or night sweats without evidence of infection Progressive marrow failure (stage III or IV disease) manifested by Hemoglobin less than 11 g/dL (anemia) AND/OR Platelet count less than 100,000/mm3 (thrombocytopenia) Autoimmune anemia and/or thrombocytopenia minimally responsive to corticosteroid therapy Massive or progressive splenomegaly Massive or progressive lymphadenopathy Progressive lymphocytosis (not due to the effects of corticosteroids) Marked hypogammaglobulinemia or development of monoclonal protein in the absence of any of the above criteria is not sufficient for eligibility

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 1.5 times ULN (unless due to hemolysis or CLL) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease No myocardial infarction in the past month Other: No uncontrolled infection No active infection with HIV (AIDS) No other malignancy within past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior interferon allowed Chemotherapy: No prior cytotoxic chemotherapy Endocrine therapy: See Disease Characteristics Prior corticosteroids, somatostatin analogues, and tamoxifen allowed Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: At least 4 weeks since prior major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259-5404
2	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
3	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
4	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa	United States	52403-1206
5	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309-1016
6	Siouxland Hematology-Oncology	Sioux City	Iowa	United States	51101-1733
7	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
8	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
9	CCOP - Duluth	Duluth	Minnesota	United States	55805
10	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
11	CentraCare Clinic	Saint Cloud	Minnesota	United States	56303
12	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
13	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
14	Quain & Ramstad Clinic, P.C.	Bismarck	North Dakota	United States	58501
15	Altru Health Systems	Grand Forks	North Dakota	United States	58201
16	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57709
17	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57105-1080