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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00089284
Recruitment Status : Terminated (Due to lack of funding, phase II of study was not completed.)
First Posted : August 5, 2004
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Northwestern University

Study Description
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Brief 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.


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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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)
Actual Study Start Date : October 28, 2003
Actual Primary Completion Date : January 2007
Actual Study Completion Date : August 20, 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) [ Time Frame: Weekly during treatment and continuing up through Day 90 ]

    The number of Dose Limiting Toxicities (DLT) observed in patients treated with Motexafin Gadolinium at different dose levels in combination with Rituxan, Indium-Zevalin, and 90Yttrium-Zevalin was used to determine the Maximum Tolerated Dose (MTD) to be used for phase II of the study. The number of dose-limiting toxicities observed in each cohort of patients determined whether to continue dose escalation. Each cohort = at least 3 patients.

    All toxicities will be graded according to the NCI Common Toxicity Criteria, version 2.0, with a DLT defined as any of the following:

    Grade 3 or 4 non-hematologic toxicity (other than grade 3 nausea or vomiting). Grade 4 vomiting despite maximal antiemetic support. Grade 4 neutropenia and thrombocytopenia either lasting longer than 14 days-Grade 4 duration will be measured (in days) from the first date in grade 4 to last date in grade 4 after nadir (growth factor and transfusion independent, respectively).


  2. Maximum Tolerated Dose (MTD) [ Time Frame: Weekly during treatment and continuing up through Day 90 ]
    The maximum tolerated dose (MTD) of Motexafin Gadolinium in combination with Rituxan, Indium-Zevalin, and 90Yttrium-Zevalin was determined using a modified Fibonacci phase I study design (with patient allocation based on amount of lymphoma bone marrow involvement) and will be used in phase II of the study. The MTD will be that dose at which 0/3 or 1/6 patients or 2/9 experience a Dose Limiting Toxicity (DLT), with the next higher dose level provoking DLT in 2/3 or 3/6 or 4/9 patients.


Secondary Outcome Measures :
  1. Anti-lymphoma Efficacy [ Time Frame: At 1, 3 and 6 months ]
    To assess the anti-lymphoma efficacy of the combination of MGd and 90Yttrium-Zevalin therapy. Disease response to treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or complete response/unconfirmed (CRu). The overall response rate (ORR) was then calculated. The time to treatment failure (TTF), overall survival (OS), and duration of response were determined.

  2. Study and Describe the Bio-locationization of Motexafin Gadolinium (MGd) in Tumors Using MRIs [ Time Frame: At baseline (pre-treatment) and on Day 4 of treatment ]
    To study the tumor-specific bio-localization of MGd in lymphoma through magnetic resonance imaging (MRI) in a subset of patients. The first 2 patients of each cohort will have MRI imaging to measure if signal intensity, a correlate for MGd uptake, is increased in known areas of lymphomatous involvement.

  3. Correlative Laboratory Studies [ Time Frame: On Day 1 and 4 ]
    To explore correlative laboratory studies of MGd (ie, uptake of MGd by peripheral mononuclear cells, effect of MGd upon peripheral lymphocyte subset populations).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00089284


Locations
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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
Robert H. Lurie Cancer Center
Investigators
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Principal Investigator: Andrew M. Evens, DO, MS Northwestern University
Principal Investigator: Leo I. Gordon, MD Northwestern University
More Information
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Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00089284    
Other Study ID Numbers: NU 02H8
1346001 ( Other Identifier: Northwestern University IRB )
First Posted: August 5, 2004    Key Record Dates
Results First Posted: August 14, 2019
Last Update Posted: August 14, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
 Motexafin gadolinium
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Photosensitizing Agents
Dermatologic Agents