Trial Information

A Phase II Multicenter Randomized 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.