RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, 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. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for non-Hodgkin's lymphoma.

PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma indolent or aggressive adult non-Hodgkin's lymphoma	Drug: fludarabine  Drug: iodine I 131 tositumomab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: radioimmunotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose of fludarabine when administered with iodine I 131 tositumomab followed by autologous peripheral blood stem cell transplantation in older patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Secondary

• Determine the overall and progression-free survival of patients treated with this regimen.
• Determine the response rate in patients treated with this regimen.
• Determine the toxicity and tolerability of this regimen in these patients.
• Determine the feasibility of this regimen in these patients.

OUTLINE: This is a dose-escalation study of fludarabine.

Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by dosimetry periodically over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab IV over 40-60 minutes on day -14. Patients also receive fludarabine IV once daily on days -11 to -9 OR days -11 or -7. Patients undergo autologous peripheral blood stem cell transplantation on day 0.

Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.

Cohorts of 4 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is estimated to be the dose that is associated with a dose-limiting toxicity rate of 25%.

After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  60 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell non-Hodgkin's lymphoma
• CD20 antigen-expressing disease
• Evidence of persistent disease by physical exam, radiographic studies, bone marrow evaluations, flow cytometry, or polymerase chain reaction
• Relapsed or refractory disease
• Failed ≥ 1 prior standard systemic therapy
• Must have had ≥ 2 x 10
• autologous CD 34-positive hematopoietic stem cells/kg harvested and cryopreserved
• Selection of CD34-positive peripheral blood stem cells (PBSC) prior to storage required (for patients with evidence of circulating lymphoma cells by flow cytometry)
• No circulating lymphoma cells by morphology or flow cytometry at or near the time of PBSC collection (for patients planning to use unpurged or unselected PBSC for transplantation)
• No small lymphocytic lymphoma or well-differentiated lymphocytic lymphoma
• No chronic lymphocytic leukemia
• No CNS lymphoma

PATIENT CHARACTERISTICS: Age

• 60 and over

Performance status

• SWOG 0-1

Life expectancy

• More than 60 days

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin < 1.5 mg/dL

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No abnormally decreased cardiac ejection fraction that would preclude bone marrow transplantation

Pulmonary

• DLCO ≥ 50% of predicted

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No AIDS
• Able to perform self-care during radiation isolation
• No circulating anti-mouse antibody
• No major infection
• No other serious medical condition that would preclude bone marrow transplantation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior bone marrow or stem cell transplantation

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy at a dose > 20 Gy to any critical normal organ, including any of the following:
• Lung
• Liver
• Spinal cord
• Greater than 25% of red bone marrow

Surgery

• Not specified

Other

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00110071

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:  CDR0000423312; FHCRC-1943.00; NCT00110071
Record last reviewed:  April 2005
Last Updated:  May 12, 2005
Record first received:  May 3, 2005
ClinicalTrials.gov Identifier:  NCT00110071
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-05-17