A Multi-Center, Open-Label, Non-Randomized Phase II Study of Elsamitrucin (SPI-28090) in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma (NHL).

Background: Elsamitrucin (SPI-28090) is a novel actinomycete fermentation product that induces single strand breaks in DNA and inhibits topoisomerase I and II. A previous Phase II trial showed evidence of promising anti-tumor activity with an acceptable toxicity profile in patients with relapsed/refractory NHL. The objectives of the current trial are to confirm and validate these earlier findings and to determine if elsamitrucin is efficacious in a particular pathologic NHL subtype(s).

Methods: Patients with relapsed or refractory NHL, indolent or aggressive, excluding HIV and Burkitt’s lymphoma were eligible for the study. Patients must have had measurable disease. All patients were given weekly Elsamitrucin 25 mg/m² i.v. administered over 5–10 minutes x 8 weeks. All patients were treated until disease progression or toxicity. Treatment was given as an outpatient.

Results: To date, 8 patients (5 males/3 females) have been enrolled on study with a median age of 70 years (range 40–83). Pathologies include diffuse large B-cell (4), diffuse mixed large B-cell (1); mantle cell (1), follicular grade 2 (1) and aggressive T-cell lymphoma (1). All patients had stage III or IV disease. The median number of prior chemotherapy regimens received was 5 (range of 2–9). A median of 4 doses (range 2–11) of Elsamitrucin have been administered to date. Myelosuppression was absent or mild in majority of the patients except for one patients that had grade 4 ANC and grade 3 thrombocytopenia. All non-hematologic toxicities were mild to moderate in severity, limited to nausea and vomiting. There were no reported liver function toxicities which was the dose limiting toxicity noted on prior Phase I trials. No drug related serious adverse events have been reported. Five patients are evaluable for response; 3 are too early to evaluate. One patient with stage IV mantle cell lymphoma who had received five prior chemotherapy regimens and radiation therapy has had a confirmed partial response after eight weeks of treatment, lasting for 8+ weeks. Another patient had unconfirmed partial response. One patient had mixed response and the other 2 had progressive disease.

Conclusions: Elsamitrucin preliminarily appears to be safe and well tolerated in this patient population. There has been some early evidence of anti-tumor activity. Accrual is ongoing and further update will be presented at the meeting.