Study Of Two Non-Myeloablative Stem Cell Transplant Strategies For Low-Grade Lymphoma And CLL

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.

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