Clinical trial NCT00089284: Phase I/II Trial of Redox Regulation in Patients With Relapsed or Refractory CD20+ NHL
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma (NHL)
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Robert H. Lurie Cancer Center
First posted: 2004-08-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Weekly during treatment and continuing up through Day 90
measure: Maximum Tolerated Dose (MTD)
timeFrame: Weekly during treatment and continuing up through Day 90
Secondary outcomes:
measure: Anti-lymphoma Efficacy
timeFrame: At 1, 3 and 6 months
measure: Study and Describe the Bio-locationization of Motexafin Gadolinium (MGd) in Tumors Using MRIs
timeFrame: At baseline (pre-treatment) and on Day 4 of treatment
measure: Correlative Laboratory Studies
timeFrame: On Day 1 and 4
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Jesse B. Brown Veterans Affairs Medical Center
state: Illinois
Study officials:
affiliation: Northwestern University
name: Andrew M. Evens, DO, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Leo I. Gordon, MD
role: PRINCIPAL_INVESTIGATOR
References: