RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving yttrium Y 90 ibritumomab tiuxetan together with fludarabine and radiation therapy before a donor stem cell transplant may be an effective treatment for non-Hodgkin''''s lymphoma.

PURPOSE: This phase II trial is studying how well giving yttrium Y 90 ibritumomab tiuxetan together with fludarabine and radiation therapy works in treating patients who are undergoing a donor stem cell transplant for relapsed or refractory B-cell non-Hodgkin''''s lymphoma.

Condition	Intervention	Phase
adult non-Hodgkin''''s lymphoma	Drug: cyclosporine  Drug: fludarabine  Drug: mycophenolate mofetil  Drug: rituximab  Drug: yttrium Y 90 ibritumomab tiuxetan  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: radioimmunotherapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the feasibility and safety of a nonmyeloablative conditioning regimen comprising yttrium Y 90 ibritumomab tiuxetan, fludarabine, and low-dose total-body irradiation followed by allogeneic peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin''''s lymphoma.
• Determine the 100-day treatment-related mortality in patients treated with this regimen.

Secondary

• Determine the potential efficacy of this regimen in these patients.
• Determine overall and progression-free survival of patients treated with this regimen.
• Determine the response rate, including molecular response, in patients treated with this regimen.
• Determine engraftment and hematopoietic adverse events in patients treated with this regimen.
• Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.

OUTLINE:

• Conditioning regimen: Patients receive rituximab IV followed, no more than 4 hours later, by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -21. Patients undergo gamma camera imaging on days -21, -19, and -18. If biodistribution is acceptable, patients receive rituximab IV followed, no more than 4 hours later, by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine IV over 30-60 minutes on days -7 to -5 and undergo low-dose total-body irradiation (TBI) on day 0.
• Allogeneic peripheral blood stem cell transplantation (PBSCT): After TBI, patients undergo allogeneic PBSCT on day 0.
• Immunosuppression: Patients who undergo PBSCT from a related donor receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). These patients also receive oral mycophenolate mofetil twice daily on days 0-27. Patients who undergo PBSCT from an unrelated donor receive oral cyclosporine twice daily on days -3 to 100 followed by a taper over 11 weeks in the absence of GVHD. These patients also receive oral mycophenolate mofetil three times daily on days 0-40 followed by a taper to day 96. After completion of study treatment, patients are followed monthly for 3 months, at 6 and 12 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell non-Hodgkin''''s lymphoma
• Relapsed or refractory disease
• Failed ≥ 1 prior standard systemic therapy
• CD20 antigen-positive disease
• Evidence of persistent disease by physical examination, radiographic studies, bone marrow evaluation, flow cytometry, or polymerase chain reaction
• No more than 25% of bone marrow involvement by lymphoma by core biopsy
• No CNS lymphoma
• Not eligible for a radioimmunotherapy-based autologous stem cell transplantation trial
• Not eligible for other therapeutic options (e.g., non-transplantation therapy or autologous stem cell transplantation) likely to have a better long-term disease-free survival with lower potential toxicity than this study
• HLA-matched identical related or unrelated donor available
• Related donor matched for HLA-A, -B, -C, and -DRB1 and to the allele level of DQB1
• No identical twins
• Unrelated donor matched for HLA-A, -B, -C, -DRB1, and -DQB1
• One allele mismatch for HLA-A, -B, or -C allowed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• SWOG 0-2 OR
• ECOG 0-2

Life expectancy

• More than 60 days

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 1.5 mg/dL

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No unstable angina

Pulmonary

• DLCO ≥ 30%
• Total lung capacity ≥ 30%
• No requirement for continuous supplemental oxygen

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• HIV negative
• No AIDS
• No major infection
• No other serious medical condition that would preclude allogeneic stem cell transplantation
• No evidence of human antimouse antibody for patients previously exposed to therapeutic murine antibodies

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 30 days since prior systemic anti-lymphoma therapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00119392

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Ajay K. Gopal, MD,  Principal Investigator,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000430649; FHCRC-1726.00; NCT00119392
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 12, 2005
ClinicalTrials.gov Identifier:  NCT00119392
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26