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

NCT00089284 | Terminated Phase 1 Results DMC

• 2 other identifiers: NU 02H81346001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Hodgkin's Lymphoma (NHL)

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

  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).

  Weekly during treatment and continuing up through Day 90

• Maximum Tolerated Dose (MTD)

  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.

  Weekly during treatment and continuing up through Day 90

Secondary Outcomes (3)

• Anti-lymphoma Efficacy

  At 1, 3 and 6 months

• Study and Describe the Bio-locationization of Motexafin Gadolinium (MGd) in Tumors Using MRIs

  At baseline (pre-treatment) and on Day 4 of treatment

• Correlative Laboratory Studies

  On Day 1 and 4

Study Arms (1)

Rituxan and 90Yttrium-Zevalin plus MGd

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.

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

Interventions

Rituxan DRUG

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.

Also known as: rituximab IDEC-C2B8

Rituxan and 90Yttrium-Zevalin plus MGd

motexafin gadolinium DRUG

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.

Also known as: MGd, Xcytrin® (motexafin gadolinium) Injection,, NSC 695238

Rituxan and 90Yttrium-Zevalin plus MGd

111Indium-Zevalin and 90Yttrium-Zevalin DRUG

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.

Also known as: Ibritumomab-tiuxetan

Rituxan and 90Yttrium-Zevalin plus MGd

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Robert H. Lurie Cancer Center: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Jesse B. Brown Veterans Affairs Medical Center

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; motexafin gadolinium; Injections; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Due to a lack of adequate funding, we were unable to complete 2 of the secondary objectives for this study.

Results Point of Contact

• Title: Clinical Research Office Administrator
• Organization: Northwestern University

cancertrials@northwestern.edu

312-695-1301

Study Officials

• Andrew M. Evens, DO, MS

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Leo I. Gordon, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: October 28, 2003
• Primary Completion: January 1, 2007
• Study Completion: August 20, 2008
• Last Updated: August 14, 2019
• Results First Posted: August 14, 2019

Record last verified: 2019-04

Locations

US (2)