RATIONALE: Monoclonal antibodies can locate cancer cells and deliver radiolabeled cancer-killing substances to them without harming normal cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of monoclonal antibodies and kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining monoclonal antibody therapy with peripheral stem cell transplantation in treating patients who have non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma indolent or aggressive adult non-Hodgkin's lymphoma	Drug: cyclophosphamide  Drug: filgrastim  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: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: radioimmunotherapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) with autologous peripheral blood stem cell rescue after in vivo purging with rituximab in patients with indolent or diffuse large B-cell non-Hodgkin's lymphoma.

OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

• Part I: Patients receive rituximab IV on days 1, 8, 15, and 22 and cyclophosphamide IV over 1 hour on day 25. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 26 and continuing until autologous peripheral blood stem cells (PBSC) are harvested.
• Beginning 4-6 weeks after completion of the fourth rituximab infusion, patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 followed by dosimetry imaging on days 1, 2, 4, and 7. Patients then receive IDEC-Y2B8 IV over 10 minutes once between days 8-15. The initial 3 patients receive the same dose of IDEC-Y2B8 and then subsequent cohorts of 3-5 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose is determined.
• Part III: All patients undergo PBSC transplantation (PBSCT) beginning after residual bone marrow radioactivity resolves. G-CSF is administered SC beginning 1 day after PBSCT and continuing until blood counts recover. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 10-30 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven indolent non-Hodgkin's lymphoma (NHL) or diffuse large B-cell lymphoma, including the following subtypes:
• Marginal zone/mucosa-associated lymphoid tissue
• Mantle cell
• Plasmacytoid
• Lymphoplasmacytoid
• Small lymphocytic
• Follicle center grades I-III (excluding chronic lymphocytic leukemia)
• Transformation from low-grade to intermediate- or high-grade allowed
• 1-5 prior chemotherapy regimens for NHL required
• Must have 0-35% bone marrow involvement with NHL on bone marrow biopsy or by flow cytometry
• No complete replacement of bone marrow with tumor
• No hypocellular bone marrow (no less than 15% cellularity) or marked decrease in 1 or more hematopoietic precursors
• Patients previously treated with anti-CD20 therapy must have achieved partial or complete response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age:

• 18 to 70

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Total lymphocyte count less than 5,000/mm^3
• Hemoglobin at least 10.0 g/dL
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 2 mg/dL (unless due to liver involvement with tumor)
• AST or ALT less than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• LVEF at least 45% by echocardiogram or MUGA

Pulmonary:

• DLCO greater than 50% of predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 2 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No active infection requiring oral or IV antibiotics
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• No prior radioimmunotherapy (e.g., yttrium Y 90 ibritumomab tiuxetan or I 131 tositumomab)
• No prior murine compounds

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior external-beam radiotherapy to more than 25% of active bone marrow (involved-field or regional)
• No prior radioimmunotherapy (e.g., yttrium Y 90 ibritumomab tiuxetan or I 131 tositumomab)

Surgery:

• Not specified

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-5256,  United States; Recruiting

Study chairs or principal investigators

Ian W. Flinn, MD, PhD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000068684; JHOC-J0004; NCI-970; NCT00017381
Record last reviewed:  April 2004
Last Updated:  December 6, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017381
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08