RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Motexafin gadolinium may increase the effectiveness of yttrium Y 90 ibritumomab tiuxetan by making the cancer cells more sensitive to the drug.

PURPOSE: This phase I/II trial is studying the side effects and best dose of motexafin gadolinium when administered with rituximab and yttrium Y 90 ibritumomab tiuxetan and to see how well they work in treating patients with stage II, stage III, or stage IV relapsed or refractory non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma indolent or aggressive adult non-Hodgkin's lymphoma	Drug: motexafin gadolinium  Drug: rituximab  Drug: yttrium Y 90 ibritumomab tiuxetan  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radioimmunotherapy  Procedure: radiosensitization	Phase I Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of motexafin gadolinium when combined with rituximab, indium In 111 ibritumomab tiuxetan (for imaging), and yttrium Y 90 ibritumomab tiuxetan in patients with bulky stage II or stage III or IV relapsed or refractory CD20-positive non-Hodgkin's lymphoma.

Secondary

• Determine the anti-lymphoma efficacy of this regimen in these patients.

OUTLINE: This is a phase I, dose-escalation study of motexafin gadolinium followed by a phase II study. Patients are stratified according to extent of lymphomatous involvement (≤ 5% vs > 5 but ≤ 24% of cellular elements).

• Patients receive motexafin gadolinium IV over 30-60 minutes on days 1-4 and 8-11. At least 1 hour after motexafin gadolinium administration, patients receive rituximab IV over 3-4 hours on days 1 and 8. After rituximab administration, patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo gamma camera scanning on days 1, 2*, 4*, and 7 and dosimetry on days 2, 4, and 7. If safe biodistribution is demonstrated, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes (after rituximab administration) on day 8. NOTE: *Patients undergo scanning after motexafin gadolinium administration on days 2 and 4.

Cohorts of 3-6 patients in each stratum receive escalating doses of motexafin gadolinium until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity (DLT) OR the dose preceding that at which 2 of 3 or 3 of 6 patients experience DLT.

• Phase II: Once the MTD is determined, additional patients are treated at that dose level as in phase I. Patients are followed weekly for 3 months and then monthly for 5 years.

PROJECTED ACCRUAL: A total of 6-30 patients will be accrued for this study within 24-30 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:
• Low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL)
• The following histologies are eligible:
• Small lymphocytic lymphoma
• Lymphoplasmacytoid lymphoma
• Follicular center grades 1, 2, or 3 lymphoma
• Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type
• Nodal marginal zone B-cell lymphoma
• Relapsed or refractory after 2 prior treatment regimens or 1 anthracycline regimen
• Diffuse large B-cell NHL or mantle cell lymphoma in first or second relapse
• Transformed NHL, defined as low-grade NHL transformed to diffuse large B-cell lymphoma, with no more than 1 relapse since transformation
• Bulky stage II (defined as lymph node > 5 cm or mediastinum > 1/3 of the diameter of the chest on plain x-ray) or stage III or IV disease
• At least 1 objectively measurable or evaluable disease site, including any of the following:
• Isolated lymph node ≥ 1.5 cm
• Enlarged spleen extending ≥ 2 cm below the left costal margin due to lymphomatous involvement
• Enlarged liver due to lymphomatous involvement by biopsy
• Monoclonal CD20-positive B-cell population in lymph nodes or bone marrow by flow cytometry
• Lymphomatous involvement of the marrow ≤ 24% of cellular elements (5% of cellular elements for the first cohort of patients)
• No hypocellular bone marrow (cellularity < 15%) or marked reduction in bone marrow precursors of one or more cell lines (i.e., granulocytic, megakaryocytic, or erythroid)
• No active CNS involvement with lymphoma 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 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• See Disease Characteristics
• Platelet count ≥ 150,000/mm^3
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• No major bleeding within the past 4 weeks

Hepatic

• See Disease Characteristics
• Bilirubin < 2 times upper limit of normal (ULN)
• AST or ALT < 2 times ULN

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• No uncontrolled hypertension
• No stroke within the past 4 weeks

Pulmonary

• DLCO ≥ 55% of predicted (corrected for hemoglobin)

Other

• No active infection
• No other active nonmalignant disease
• No known G6PD deficiency
• No history of porphyria
• No other condition that would preclude study participation
• No human anti-mouse antibodies
• No known history of HIV
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Recovered from prior immunotherapy
• No prior myeloablative therapy with allogeneic or autologous bone marrow transplantation or peripheral blood stem cell rescue
• No prior radioimmunoconjugate therapy
• No prior exposure to murine antibodies other than rituximab
• More than 4 weeks since prior rituximab
• No history of failed stem cell collection

Chemotherapy

• See Disease Characteristics
• See Biologic therapy
• Recovered from prior chemotherapy
• More than 6 weeks since prior nitrosoureas or mitomycin

Endocrine therapy

• No concurrent systemic corticosteroids
• Topical steroids or steroids for allergy prophylaxis before imaging procedures allowed

Radiotherapy

• See Biologic therapy
• Recovered from prior radiotherapy
• No prior external beam radiotherapy to ≥ 25% of bone marrow

Surgery

• More than 4 weeks since prior major surgery and recovered

Other

• More than 4 weeks since prior anticancer therapy

Illinois
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting

Study chairs or principal investigators

Andrew M. Evens, DO, MS,  Principal Investigator,  Robert H. Lurie Cancer Center   
Leo I. Gordon, MD,  Principal Investigator,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000378192; NU-02H8; NU-0228-024; PCI-P-PCYC-0213; NCT00089284
Record last reviewed:  February 2005
Last Updated:  February 15, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089284
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08