RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus may prevent this from happening.

PURPOSE: Randomized phase II trial to compare the effectiveness of fludarabine plus total-body irradiation with that of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have relapsed non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
Waldenstrom's Macroglobulinemia refractory chronic lymphocytic leukemia recurrent grade I follicular small cleaved cell lymphoma recurrent grade II follicular mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent diffuse small lymphocytic/marginal zone lymphoma	Drug: allogeneic lymphocytes  Drug: cyclophosphamide  Drug: cyclosporine  Drug: fludarabine  Drug: methotrexate  Drug: mycophenolate mofetil  Drug: tacrolimus  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the 1-year overall survival rate of patients with relapsed low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with fludarabine and total body irradiation vs cyclophosphamide and fludarabine followed by allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusions.
• Compare the toxic effects of these regimens in these patients.
• Compare the incidence and severity of acute and chronic graft-versus-host disease in patients treated with these regimens.
• Compare the 1-year treatment-related mortality and infectious complications in patients treated with these regimens.
• Compare the efficacy of these treatment regimens, in terms of 1-year disease-free survival, of these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease, age (less than 55 vs over 55), and participating transplantation center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation followed by allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising oral cyclosporine twice daily on days -2 to 90 followed by a taper on days 90-150 and oral mycophenolate mofetil twice daily on days 0-28.
• Arm II: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on days -3 to -2. Patients undergo PBSCT on day 0. Patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and tacrolimus IV continuously and then orally on days -2 to 90 followed by a taper on days 90-150. At approximately day 180, patients with persistent disease, evidence of T-cell chimerism, and no GVHD may receive up to 3 donor lymphocyte infusions administered every 1-2 months.

Quality of life is assessed at baseline, 1 month, every 3 months for 1 year, and then every 6 months for 1 year.

Patients are followed at 1 month, every 3 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia OR
• Diagnosis of non-Hodgkin's lymphoma
• Lymphoplasmacytic lymphoma
• Grade I follicular small cleaved cell lymphoma
• Grade II follicular mixed cell lymphoma
• Diffuse small cleaved cell lymphoma
• Small lymphocytic lymphoma
• Relapsed after at least 1 course of prior therapy
• Availability of a 6/6 HLA A, B, and DR identical sibling donor
• Nonmyeloablative transplantation candidate
• No clinically significant effusions or ascites that would preclude administration of methotrexate

PATIENT CHARACTERISTICS: Age:

• 18 to 75

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 3 mg/dL

Renal:

• Creatinine no greater than 2 mg/dL

Cardiovascular:

• LVEF at least 40% on MUGA scan or echocardiogram

Pulmonary:

• DLCO at least 50% of predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled bacterial, viral, fungal, or parasitic infection
• HIV1 and HIV2 negative
• No other active malignancy except basal cell skin cancer
• No recent history of drug or alcohol abuse
• No other primary disease or comorbid illness that would severely limit life expectancy

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• Prior autologous bone marrow transplantation allowed if disease has progressed after transplantation
• No entry on study as part of a tandem autologous transplantation followed by nonmyeloablative allograft protocol

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Colorado
      Rocky Mountain Cancer Centers, Denver,  Colorado,  80218,  United States
Delaware
      Delaware Clinical & Laboratory Physicians, Newark,  Delaware,  19713,  United States
Florida
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Georgia
      Blood and Marrow Transplant Group of Georgia, Atlanta,  Georgia,  30342-1601,  United States
Iowa
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
Missouri
      University of Missouri Kansas City School of Medicine, Kansas City,  Missouri,  64111,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States
New York
      James P. Wilmot Cancer Center, Rochester,  New York,  14642,  United States
Oregon
      Oregon Cancer Institute, Portland,  Oregon,  97239,  United States
Pennsylvania
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37212,  United States
Texas
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-8590,  United States
      Texas Transplant Institute, San Antonio,  Texas,  78229,  United States
Virginia
      Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States
Canada, Ontario
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M4S 1KN,  Canada
      University of Toronto, Toronto,  Ontario,  M5S 1A8,  Canada
Canada, Quebec
      Hopital du Saint-Sacrament, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada

Study chairs or principal investigators

Robert H. Collins, MD,  Study Chair,  Simmons Cancer Center   

Study ID Numbers:  CDR0000069462; UTSMC-0501228; AMGEN-UTSMC-0501228; IBMTR-SC-00-02.1; ROCHE-UTSMC-0501228; SPRI-UTSMC-0501228; NCI-V02-1706
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00041288
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08