RATIONALE: Radiolabeled monoclonal antibodies such as yttrium Y90 ibritumomab tiuxetan can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining yttrium Y90 ibritumomab tiuxetan and chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining yttrium Y90 ibritumomab tiuxetan with high-dose chemotherapy followed by autologous stem cell transplantation in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma	Drug: carmustine  Drug: cytarabine  Drug: etoposide  Drug: filgrastim  Drug: melphalan  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: high-dose 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:

• Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan, in terms of absorbed radiation to critical organs, when administered with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
• Determine whether the residual radioactivity detected at the time of stem cell reinfusion affects the reinfused cells and delays engraftment in patients treated with this regimen.
• Determine the duration of response and survival of patients treated with this regimen.

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

• Patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -22. Patients then receive rituximab IV and IDEC-Y2B8 IV over 10 minutes on day -14. Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
• High-dose conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 2 hours twice daily and cytarabine IV over 1 hour twice daily on days -5 to -2, and melphalan IV over 1 hour on day -1.
• Autologous stem cell transplantation: Autologous peripheral blood stem cells are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover. Patients are followed at 30 days, 3 and 6 months, and then annually for 5 years.

PROJECTED ACCRUAL: A maximum of 42 patients will be accrued for this study.

Ages Eligible for Study:  17 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell non-Hodgkin's lymphoma
• Relapsed or refractory disease
• CD20-positive disease
• Must have received at least 1 prior treatment regimen
• Complete remission with prior conventional salvage chemotherapy is allowed
• No more than 25% lymphoma in bone marrow
• No circulating malignant cells on blood smear
• No CNS involvement by lymphoma
• No HIV- or AIDS-related lymphoma

PATIENT CHARACTERISTICS: Age

• Over 17

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3

Hepatic

• Transaminases less than 2 times normal

Renal

• Creatinine clearance greater than 50 mL/min

Cardiovascular

• LVEF at least 45%

Pulmonary

• Corrected DLCO at least 70% of predicted
• FEV_1 or FVC greater than 60%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No serious nonmalignant disease or other condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior rituximab and recovered
• No other prior murine antibodies
• No prior stem cell transplantation
• No prior radioimmunoconjugate therapy

Chemotherapy

• See Disease Characteristics
• More than 6 weeks since prior nitrosoureas or mitomycin and recovered

Endocrine therapy

• No concurrent systemic corticosteroids

Radiotherapy

• Recovered from prior radiotherapy
• No prior external beam irradiation to more than 25% of the active bone marrow

Surgery

• More than 4 weeks since prior major surgery and recovered

Other

• More than 3 weeks since prior anticancer therapy

Illinois
      Hematology-Oncology Associates of Illinois, Chicago,  Illinois,  60611-2998,  United States; Recruiting
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Jane N. Winter, MD,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000287244; NU-99H11; IDEC-NU99H11; NCT00058292
Record last reviewed:  October 2004
Last Updated:  December 6, 2004
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00058292
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08