Overview

This trial is active, not recruiting.

Condition non-hodgkin's lymphoma (nhl)
Treatments rituxan, motexafin gadolinium, 111indium-zevalin and 90yttrium-zevalin
Phase phase 1/phase 2
Target CD20
Sponsor Northwestern University
Start date September 2003
End date December 2007
Trial size 30 participants
Trial identifier NCT00089284, 1346001, NU 02H8

Summary

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.

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
rituxan rituximab IDEC-C2B8
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.
motexafin gadolinium MGd, Xcytrin® (motexafin gadolinium) Injection,
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.
111indium-zevalin and 90yttrium-zevalin Ibritumomab-tiuxetan
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.

Primary Outcomes

Measure
Maximum tolerated dose
time frame: On each treatment day (2, 3, 4, 9, 10, 11) and Day 7 evaluation

Secondary Outcomes

Measure
Anti-lymphoma efficacy
time frame: At 1, 3 and 6 months
Study location of tumor through MRIs
time frame: At 1,3 and 6 months
Correlative laboratory studies
time frame: On Day 1 and 4

Eligibility Criteria

Male or female participants at least 18 years old.

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 Age 18 and over Recovered from prior immunotherapy Life expectancy At least 3 months Recovered from prior chemotherapy - More than 4 weeks since prior major surgery and recovered - More than 4 weeks since prior anticancer therapy recovered from prior radiotherapy Exclusion criteria: No major bleeding within the past 4 weeks No uncontrolled hypertension No stroke within the past 4 weeks - 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 - 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

Additional Information

Official title A Phase I/II Trial of Redox Regulation in Patients With Relapsed or Refractory CD20 Positive Non-Hodgkin's Lymphoma (NHL): Combining 90-Yttrium- Zevalin and the Redox- Modulating Agent, Motexafin Gadolinium (MGd)
Principal investigator Andrew M. Evens, DO, MS
Description 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). 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. - 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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2011.
Information provided to ClinicalTrials.gov by Northwestern University.