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

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Abstract Background: Elsamitrucin (SPI-28090) is a novel topoisomerase I and II inhibitor. An earlier small study with Elsamitrucin, conducted prior to the introduction of rituximab, showed anti-tumor activity in patients with relapsed or refractory NHL with an acceptable toxicity profile. The objectives of this current trial are to validate these earlier findings and to generate data in patients with relapsed or refractory NHL who had previously received rituximab-based chemotherapy. Methods: Three groups of relapsed or refractory NHL were enrolled: G1: chronic or small B-lymphocytic lymphoma/leukemia; G2: indolent lymphoma (follicular/diffuse small cell or mixed); and G3: large cell or mantle cell lymphoma. Patients were treated with weekly Elsamitrucin 25 mg/m2 IV administered over 5–10 minutes. All patients were treated until disease progression or toxicity. Results: 55 patients (34 males/21 females) have been enrolled; median age was 70 years (range 40–84). All patients had stage III or IV disease. Most patients were heavily pretreated with a median of 4 (1–8) prior chemotherapy regimens; 54 out of 55 patients had rituximab-based chemotherapy. Other study characteristics and results are shown on Table 1. One PR occurred in a mantle cell lymphoma patient who had received five prior chemotherapy regimens and lasting for 27 weeks. Minor responses have been documented in several patients still on therapy. Most side effects were mild to moderate in severity and consisted of nausea (51%), fatigue (42%), anorexia (22%), vomiting (16%) and cellulitis (11%). Myelosuppression was uncommon: grade 3 or 4 neutropenia was reported in 2 patients, grade 3 anemia and thrombocytopenia reported in 1 patient each. There was one patient who had moderate transient increase in transaminase level. No drug related serious adverse events have been reported. Conclusions: Elsamitrucin appears to be safe and well tolerated over periods of up to 47 weeks in these patients lymphoma. There is evidence of anti-tumor activity in this very heavily pretreated patient population. With 2 PR, several minor responses and durable stable disease observed. In view of the minimal toxicities in particular myelosuppression, we plan to combine elsamitrucin with one or more active agents in less heavily pretreated patients. Table 1 CLL/SLL (G1) Indolent (G2) Aggressive (G3) TTP means time to progression N 14 24 17 Median LDH (U/L) 244 253 242 Median # of doses (range) 8 (2–24) 15 (4–46) 4 (1–27) Best Response PR (%) − 1 (4%) 1 (6%) MR (%) 2 (14%) 6 (25%) 1 (6%) SD (%) 9 (64%) 12 (50%) 4 (24%) TTP (days) 98.5 138 34 Range 21–216 21–330 2–245

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