Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Dermatologic Agents

Rituximab

Motexafin gadolinium

Antineoplastic Agents, Immunological

Immunologic Factors

Photosensitizing Agents

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.

Rituxan

motexafin gadolinium

111Indium-Zevalin and 90Yttrium-Zevalin

Andrew M. Evens, DO, MS

Leo I. Gordon, MD

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.

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.

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

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)

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).

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.

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.

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.

To explore correlative laboratory studies of MGd (ie, uptake of MGd by peripheral mononuclear cells, effect of MGd upon peripheral lymphocyte subset populations).

Robert H. Lurie Cancer Center

Northwestern University

1 patient was withdrawn from the study without receiving any Zevalin (Y90) and thus was not considered evaluable for toxicity/adverse events.

For the phase I dose-escalation portion, patients were allocated based on the amount of lymphoma bone marrow involvement. Initially, enrollment to the first cohort (2.5 mg/kg MGd) was open only to those with ≤ 5% of bone marrow involvement.

2.5 mg/kg MGd & ≤ 5% Bone Marrow Involvement

In the phase I portion of the study, following completion of enrollment of patients with ≤ 5% bone marrow involvement to their first cohort (2.5 mg/kg MGd), patients with 6-24% bone marrow involvement could be enrolled to their first cohort (2.5 mg/kg MGd).

2.5 mg/kg MGd & 6-24% Bone Marrow Involvement

After completion of the first cohort (2.5 mg/kg MGd) in the ≤ 5% Bone Marrow Involvement group, patients with ≤ 5% Bone Marrow Involvement were enrolled to the second cohort (3.5 mg/kg MGd).

3.5 mg/kg MGd & ≤ 5% Bone Marrow Involvement

After completion of the second cohort (3.5 mg/kg MGd) in the ≤ 5% Bone Marrow Involvement group, patients with ≤ 5% Bone Marrow Involvement were enrolled to the third cohort (5.0 mg/kg MGd).

5.0 mg/kg MGd & ≤ 5% Bone Marrow Involvement

After completion of the first cohort (2.5 mg/kg MGd) in the ≤ 6-24% Bone Marrow Involvement group, patients with ≤ 6-24% Bone Marrow Involvement were enrolled to the second cohort (3.5 mg/kg MGd).

3.5 mg/kg MGd & 6-24% Bone Marrow Involvement

After completion of the second cohort (3.5 mg/kg MGd) in the ≤ 6-24% Bone Marrow Involvement group, patients with ≤ 6-24% Bone Marrow Involvement were enrolled to the third cohort (5.0 mg/kg MGd).

5.0 mg/kg MGd & 6-24% Bone Marrow Involvement

Phase I: 2.5 mg/kg MGd & ≤ 5% Bone Marrow Involvement

Phase I: 2.5 mg/kg MGd & 6-24% Bone Marrow Involvement

Phase I: 3.5 mg/kg MGd & ≤ 5% Bone Marrow Involvement

Phase I: 5.0 mg/kg MGd & ≤ 5% Bone Marrow Involvement

After completion of the Phase I portion, patients were enrolled to the maximum tolerated dose (MTD) group of 5.0 mg/kg MGd for \</+ 5% Bone Marrow Involvement.

Phase II: 5.0 mg/kg MGd & </= 5% Bone Marrow Involvement

Total

Age, Categorical

Sex: Female, Male

All patients were assigned race at the time of registration according to how their race is listed in their medical records.

Race (NIH/OMB)

United States

Region of Enrollment

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

Clinical Research Office Administrator

For the phase I dose-escalation portion, patients were allocated based on the amount of lymphoma bone marrow involvement. Initially, enrollment to the first cohort was open only to those with ≤ 5% of bone marrow involvement.

In the phase I portion of the study, following completion of enrollment of patients with ≤ 5% bone marrow involvement to the first cohort on the Lesser Bone Marrow Involvement arm, patients with 6-24% bone marrow involvement could be enrolled to the first cohort in the Greater Bone Marrow Involvement arm.

Following completion of enrollment to the first cohort, patients with ≤ 5% bone marrow involvement were then enrolled to the second cohort (3.5 mg/kg MGd).

Following completion of enrollment to the second cohort, patients with ≤ 5% bone marrow involvement were then enrolled to the third cohort (5.0 mg/kg MGd).

Following completion of enrollment to their first cohort, patients with 6-24% bone marrow involvement were then enrolled to their second cohort (3.5 mg/kg MGd).

Following completion of enrollment to their second cohort, patients with 6-24% bone marrow involvement were then enrolled to their third cohort (5.0 mg/kg MGd).

Only patients enrolled during the phase I portion of this trial were analyzed for this outcome measure.

Dose Limiting Toxicities (DLT)

Rituxan and 90Yttrium-Zevalin Plus MGd

Phase I arms were evaluable for this outcome measure.

Maximum Tolerated Dose (MTD)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Complete Response/Uncofirmed (CRu)

All phase I and phase II patients were evaluated for response to treatment (anti-lymphoma efficacy). For the cohort with ≤ 5% bone marrow involvement treated at the 5.0 mg/kg MGd dose, results are based on 6 phase I patients and 8 phase II patients. 2 patients were determined not to be evaluable as they did not reach response time points.

Anti-lymphoma Efficacy

Phase I: 3.5 mg/kg MGd & 6-24% Bone Marrow Involvement

Phase I: 5.0 mg/kg MGd & 6-24% Bone Marrow Involvement

Data was not collected for analysis of this outcome measure due to lack of funding.

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

Data not collected for analysis of this outcome measure.

Spots Global Cancer Trial Database for Phase I/II Trial of Redox Regulation in Patients With Relapsed or Refractory CD20+ NHL

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