Phase I/II Trial of Redox Regulation in Patients With Relapsed or Refractory CD20+ NHL

Northwestern University

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Non-Hodgkin's Lymphoma (NHL)

Treatments: Drug: Rituxan; Drug: motexafin gadolinium; Drug: 111Indium-Zevalin and 90Yttrium-Zevalin

Study type: Interventional

Funder types: Other

Identifiers

NCT00089284

1346001 (Other Identifier)

NU 02H8

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Rituxan and 90Yttrium-Zevalin plus MGd

Experimental group

Description:

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.

Treatment:

Drug: motexafin gadolinium

Drug: 111Indium-Zevalin and 90Yttrium-Zevalin

Drug: Rituxan