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Phase III Randomized Trial of Fludarabine and Cyclophosphamide Versus Fludarabine for Previously Untreated Chronic Lymphocytic Leukemia

Phase 3
18 Years
Not Enrolling

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Trial Information

Phase III Randomized Trial of Fludarabine and Cyclophosphamide Versus Fludarabine for Previously Untreated Chronic Lymphocytic Leukemia


- Compare the efficacy of fludarabine with or without cyclophosphamide in terms of
complete remission rate and overall survival in patients with previously untreated B
cell chronic lymphocytic leukemia (CLL).

- Compare the toxicities of these 2 regimens in this patient population.

- Determine whether the expression of proteins specifically implicated in the regulation
of DNA damage induced apoptosis of lymphoid cells (i.e., p53; mdm2; GST; Bcl-2; Mcl-1;
Bax; p27; and caspase-3) correlates with response to chemotherapy in these patients.

- Determine whether there is a relationship between clinical response or resistance and
differential expression of genes in the CLL cells either at initiation of therapy or
following relapse and progression.

- Correlate mutations in immunoglobulin heavy chain variable region genes with clinical
response or resistance in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to stage
of disease (O-II vs III-IV). Patients are randomized to one of two treatment arms.

- Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5.

- Arm II: Patients receive fludarabine as in arm I plus cyclophosphamide IV over 1 hour
on day 1.

Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months until disease

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study over 2 to 2.5

Inclusion Criteria


- Diagnosis of chronic lymphocytic leukemia (CLL) of any stage as defined by the

- Peripheral blood absolute lymphocyte count greater than 5,000/mm^3 within 14
days prior to study

- Lymphocytes must be small to moderate size with no more than 55% prolymphocytes,
atypical lymphocytes, or lymphoblasts morphologically

- Phenotypically characterized as B-CLL

- Must have one of the following characteristics indicating need for chemotherapy:

- Progressive marrow failure (hemoglobin less than 10 g/dL and/or platelet count
less than 100,000/mm^3)

- Progressive lymphocytosis with an increase of more than 50% over a 2 month
period or anticipated doubling time of less than 6 months

- Massive (i.e., greater than 6 cm below left costal margin) or progressive

- Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or
progressive adenopathy

- At least 10% weight loss within 6 months of study

- Extreme fatigue

- Fevers greater than 100.5 degrees F for 2 weeks without evidence of infection

- Night sweats without evidence of infection

- No autoimmune anemia or autoimmune thrombocytopenia



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified


- See Disease Characteristics


- Bilirubin no greater than 2 mg/dL unless secondary to tumor


- Creatinine no greater than 2.0 mg/dL

- Creatinine clearance at least 40 mL/min if creatinine is greater than 1.5 mg/dL


- No other prior or concurrent malignancy within the past 2 years except basal cell
carcinoma of the skin or carcinoma in situ of the cervix

- No active infection requiring oral or intravenous antibiotics

- Not pregnant or nursing

- Fertile patients must use effective contraception


Biologic therapy:

- Not specified


- No prior cytotoxic chemotherapy

Endocrine therapy:

- No prior steroid treatment for CLL


- Not specified


- Not specified

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Ian W. Flinn, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 1999

Completion Date:

Related Keywords:

  • Leukemia
  • stage 0 chronic lymphocytic leukemia
  • 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
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



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