Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Motexafin Gadolinium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage II, Stage III, or Stage IV Relapsed or Refractory Non-Hodgkin's Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Temporarily closed 18 and over NCI, Pharmaceutical / Industry NU-02H8 NU-0228-024, PCI-P-PCYC-0213, NCT00089284

Objectives

Primary

1. 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

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

Entry 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.]

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

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/mm³
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• 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

Expected Enrollment

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

Outcomes

Maximum tolerated dose
Dose-limiting toxicity

Anti-lymphoma efficacy

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).

• Phase I: 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.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Andrew Evens, DO, MS, Principal investigator		Ph: 312-695-4537 Email: a-evens@northwestern.edu
Leo Gordon, MD, Principal investigator		Ph: 312-695-4546 Email: l-gordon@northwestern.edu

Registry 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)
Trial Start Date		2003-09-10
Trial Completion Date		2008-04-01 (estimated)
Registered in ClinicalTrials.gov		NCT00089284
Date Submitted to PDQ		2004-07-02
Information Last Verified		2008-04-20
NCI Grant/Contract Number		CA60553