BOUDRY, Switzerland--(December 10, 2008)--Celgene International Sarl (NASDAQ: CELG) reported that results of a Phase I study presented today combining REVLIMID and VIDAZA in patients with higher-risk myelodysplastic syndromes (MDS) found that the combination of these two therapies is well tolerated and has high activity. The data were reported during the 50th Annual Meeting of the American Society of Hematology.
"Lenalidomide and azacitidine have demonstrated significant activity as single agents in lower- and higher-risk MDS patients respectively," said Mikkael A. Sekeres, M.D. Cleveland Clinic Taussig Cancer Institute, the lead investigator of the study and consultant to Celgene. "By combining the immunomodulatory, anti-angiogenic and cytotoxic properties of lenalidomide and the DNA demethylating and cytotoxic activities of azacitidine we expect greater efficacy in patients with MDS and AML. These results report a well-tolerated and effective regimen."
Six total dosing cohorts were employed across the study and incorporating the safety and efficacy data, the optimal dose of the combination regimen appears to be azacitidine 75 mg/m2 SC days 1-5 and lenalidomide 10 mg PO days 1-21. In this cohort of three patients, there were no grade 3/4 non-hematologic toxicities and the maximum response was two patients with a complete response and one with stable disease.
Of 18 patients evaluable for response, 39 percent of patients (7 patients) exhibited a complete response with an overall response rate of 72 percent (13 patients).
The Phase I, multi-center clinical study sought to determine the safety of the combination therapy, the maximum tolerated dose and dose-limiting toxicities. The combination was well tolerated with no dose-limiting toxicities occurring in any dosing cohort. The median decrease in absolute neutrophil count (ANC) was 26 percent and the median platelet decrease was zero percent (mean = 24%) within the first eight weeks.
Grade 3/4 non-hematologic toxicities included cardiac (2), monocular blindness (1), basal cell skin carcinoma (1), CNS hemorrhage (2), febrile neutropenia (5), shortness of breath (1), renal failure (1) and perforated appendix (1). Although cycle two was delayed for five patients, there were no dose reductions for toxicities
Additionally, the study evaluated response to the therapy according to the modified International Working Group response criteria. Higher-risk MDS patients previously untreated with azacitidine or lenalidomide were enrolled in the trial using a 3 + 3 dose escalation design with cycles lasting 28 days to a maximum of seven cycles.
Source: Celgene International Sàrl