Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

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.

Sex

All

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

• RESULTElse M, Cocks K, Crofts S, Wade R, Richards SM, Catovsky D, Smith AG; UK National Cancer Research Institute (NCRI) Chronic Lymphocytic Leukaemia Trials Group. Quality of life in chronic lymphocytic leukemia: 5-year results from the multicenter randomized LRF CLL4 trial. Leuk Lymphoma. 2012 Jul;53(7):1289-98. doi: 10.3109/10428194.2011.649479. Epub 2012 Mar 1. PMID 22168274
• RESULTGonzalez D, Martinez P, Wade R, Hockley S, Oscier D, Matutes E, Dearden CE, Richards SM, Catovsky D, Morgan GJ. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J Clin Oncol. 2011 Jun 1;29(16):2223-9. doi: 10.1200/JCO.2010.32.0838. Epub 2011 Apr 11. PMID 21483000
• RESULTWade R, Di Bernardo MC, Richards S, Rossi D, Crowther-Swanepoel D, Gaidano G, Oscier DG, Catovsky D, Houlston RS. Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial. Haematologica. 2011 Oct;96(10):1496-503. doi: 10.3324/haematol.2011.043471. Epub 2011 Jun 9. PMID 21659360
• RESULTOscier D, Wade R, Davis Z, Morilla A, Best G, Richards S, Else M, Matutes E, Catovsky D; Chronic Lymphocytic Leukaemia Working Group, UK National Cancer Research Institute. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation. Haematologica. 2010 Oct;95(10):1705-12. doi: 10.3324/haematol.2010.025338. Epub 2010 May 29. PMID 20511662
• RESULTElse M, Smith AG, Cocks K, Richards SM, Crofts S, Wade R, Catovsky D. Patients' experience of chronic lymphocytic leukaemia: baseline health-related quality of life results from the LRF CLL4 trial. Br J Haematol. 2008 Dec;143(5):690-7. doi: 10.1111/j.1365-2141.2008.07407.x. Epub 2008 Oct 18. PMID 19016733
• RESULTCatovsky D, Richards S, Matutes E, Oscier D, Dyer M, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-239. doi: 10.1016/S0140-6736(07)61125-8.