Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for chronic lymphocytic leukemia. PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared to fludarabine and cyclophosphamide or fludarabine alone in treating patients with newly diagnosed chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide. Compare the response rate and duration of remission in patients treated with these regimens. Compare the toxic effects of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients. Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens. OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization. Depending on response, some patients may also participate in a second randomization to one of two treatment arms. First randomization: Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year. Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization. Second randomization: Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay. Arm II: Treatment is physician's choice, which may include any of the options in arm I. Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter. Patients are followed annually for survival. PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study within 6-7 years.

Official Title
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Chronic Lymphocytic Leukemia Trial 4: A Randomized Comparison of Chlorambucil, Fludarabine and Fludarabine Plus Cyclophosphamide

Conditions
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Leukemia

Intervention / Treatment
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* Drug: chlorambucil
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: fludarabine phosphate
* Drug: prednisolone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (CLL) requiring therapy and meeting the following criteria: Previously untreated disease Peripheral blood morphology, excluding other leukemia and low-grade lymphoma in leukemic phase Cell markers: CD5+, CD23+, SmIg (weak), CD79b-, FMC7- Persistent lymphocytosis (greater than 10,000/mm^3) At least 40% bone marrow infiltration Stage 0 or I progressive disease indicated by at least one of the following: Persistent rise in lymphocyte count with doubling time less than 12 months Downward trend in hemoglobin and/or platelet count At least 50% increase in size of liver and/or spleen and/or lymph nodes Appearance of lymphadenopathy, hepatomegaly, or splenomegaly Constitutional symptoms caused by disease Pyrexia Night sweats Weight loss OR Stage II or III PATIENT CHARACTERISTICS: Age: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN)* SGOT/SGPT no greater than 2 times ULN* NOTE: * Unless due to CLL Renal: Creatinine clearance at least 30 mL/min Other: No other cancer or life-threatening disease Not pregnant Fertile patients must use effective contraception during and for 6 months after study therapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No concurrent corticosteroids (e.g., dexamethasone) as antiemetics Radiotherapy Not specified Surgery Not specified
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: chlorambucil|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: fludarabine phosphate|nan|
|Drug: prednisolone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia