This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To assess the clinical response rate (complete response [CR], unconfirmed complete response [CRu], and partial response [PR]), to Motexafin Gadolinium (MGd) in patients with relapsed or refractory indolent non-Hodgkin's Lymphoma (NHL) Secondary; -To assess the combined clinical benefit rate (CR, CRu, and PR, stable disease [SD]) -To assess progression-free survival -To assess duration of clinical response -To evaluate the safety and tolerability of MGd in this patient population Study Design: A one-arm, open-label, Phase II study based on a Simon 2-Stage design enrolling approximately 15 patients in Stage 1 and 20 patients in Stage 2, for a total of 35 patients. The study will consist of up to six 28-day cycles, or 168 days, with a follow-up period of up to 1 yr for patients showing clinical benefit. Patients who meet the eligibility criteria will be enrolled sequentially and treated daily with 6.0 mg/kg MGd on days 1 through 3 (Treatment A) and days 15 through 17 (Treatment B) of each 28-day cycle. Patients will be evaluated for response between days 21 and 28 of cycles 2, 4, and 6. Patients will be followed until disease progression, disease relapse, or for one year after treatment is completed. Patients with progressive disease (PD) or relapsed disease (RD) at any time will be terminated from the study. Duration: Enrollment will be completed in approximately 1 yr. Individual patients will participate in the study for up to 18 months. Study Population: Adults with refractory or relapsed indolent NHL with Eastern Cooperative Oncology Group (ECOG) performance status scores of 0, 1, or 2. Endpoints: Primary: -Clinical response rate (CR, CRu, PR) to MGd in patients with relapsed or refractory indolent NHL Secondary: -Clinical benefit rate (CR, CRu, PR, SD) -Progression-free survival -Duration of clinical response -Safety and tolerability of MGd in the treatment of indolent NHL Investigational Drug: MGd 6.0 mg/kg/day administered intravenously (IV) once a day (q d) on Treatment A, Days 1 through 3, and Treatment B, days 15 through 17, of each 28-day cycle, over 30 minutes. Visit Schedule: Screening visit within 14 days of first dose. Treatment visits: Once daily on Days 1 through 3 (Treatment A) and Days 15 through 17 (Treatment B) of each 28-day cycle and once for response evaluation between days 21 and 28 of Cycles 2, 4, and 6. Follow-up visits: Patients with CR, CRu, PR, and SD: Every 60 days after completion of the first MGd dose of Cycle 6 for 1 yr. Patients with PD, RD, or who terminate before study completion: 30 days after the last MGd dose or termination. Safety follow-up: At least 30 days after completion of the last MGd dose. Overall Study Design and Plan: This Phase II trial will evaluate the clinical response rate resulting from the use of MGd in approximately 35 patients with relapsed or refractory indolent NHL. The trial design is based on a Simon 2-stage clinical trial design, 24 Clinical benefit rate, overall progression-free survival, clinical response duration, and safety of this treatment therapy will also be explored. Patients will be monitored for safety (including adverse events [AEs]) throughout the treatment and safety follow-up periods. All patients must have refractory or relapsed indolent NHL as defined by the following: -Refractory disease, defined as disease progression during most recent systemic therapy or no response (less than PR) to most recent systemic therapy -Relapsed disease, defined as progressive disease after having responded to most recent systemic therapy. Patients who meet the eligibility criteria will be enrolled sequentially and treated daily with 6.0 mg/kg MGd on days 1 through 3 (Treatment A) and days 15 through 17 (Treatment B) of each 28-day cycle. Patients will be evaluated for clinical response between days 21 and 28 of Cycles 2, 4, and 6. Patients whose disease has not progressed or relapsed will continue on the study for a maximum of six cycles. Patients with (PD) or (RD) will be terminated from the study. Patients whose disease does not progress and who do not complete Cycle 2 Treatment B and follow-up disease assessments will be replaced. If fewer than two of the 15 patients in Stage 1 exhibit response (CR, CRu, or PR), the study will not proceed to Stage 2. Otherwise, patient enrollment for Stage 2 will begin as soon as the last patient in Stage 1 has been enrolled. In Stage 2, an additional 20 patients will be enrolled and treated following the same treatment regimen and assessment schedule as in Stage 1.
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