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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Northwestern University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00089284
First received: August 4, 2004
Last updated: April 11, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma (NHL)
Drug: Rituxan
Drug: motexafin gadolinium
Drug: 111Indium-Zevalin and 90Yttrium-Zevalin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: On each treatment day (2, 3, 4, 9, 10, 11) and Day 7 evaluation ] [ Designated as safety issue: Yes ]
    To determine the maximally tolerated dose and dose-limiting toxicity of MGd in combination with Rituxan, 111Indium-Zevalin, and 90Yttrium- Zevalin using a modified Fibonacci phase I study design (with patient allocation based on amount of lymphoma bone marrow involvement


Secondary Outcome Measures:
  • Anti-lymphoma efficacy [ Time Frame: At 1, 3 and 6 months ] [ Designated as safety issue: No ]
    To assess the anti-lymphoma efficacy of the combination of MGd and 90Yttrium-Zevalin therapy.

  • Study location of tumor through MRIs [ Time Frame: At 1,3 and 6 months ] [ Designated as safety issue: No ]
    To study the tumor-specific bio-localization of MGd in lymphoma through magnetic resonance imaging (MRI) in a subset of patients

  • Correlative laboratory studies [ Time Frame: On Day 1 and 4 ] [ Designated as safety issue: No ]
    To explore correlative laboratory studies of MGd (ie, uptake of MGd by peripheral mononuclear cells, effect of MGd upon peripheral lymphocyte subset populations).


Enrollment: 30
Study Start Date: September 2003
Estimated Study Completion Date: April 2012
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituxan and 90Yttrium-Zevalin plus MGd
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.
Drug: Rituxan
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.
Other Name: rituximab IDEC-C2B8
Drug: motexafin gadolinium
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.
Other Names:
  • MGd, Xcytrin® (motexafin gadolinium) Injection,
  • NSC 695238
Drug: 111Indium-Zevalin and 90Yttrium-Zevalin
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.
Other Name: Ibritumomab-tiuxetan

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00089284

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611-3013
Jesse B. Brown Veterans Affairs Medical Center
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Andrew M. Evens, DO, MS Northwestern University
Principal Investigator: Leo I. Gordon, MD Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Andrew Evens, Northwestern University
ClinicalTrials.gov Identifier: NCT00089284     History of Changes
Other Study ID Numbers: NU 02H8, 1346001
Study First Received: August 4, 2004
Last Updated: April 11, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antibodies, Monoclonal
Motexafin gadolinium
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Photosensitizing Agents
Radiation-Sensitizing Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on April 15, 2014