A Phase I/II Study with CP-4055 in Patients with Haematologic Malignancies.

Background: CP-4055 (ELACYT™, cytarabine 5′-elaidic acid ester) is a novel cytotoxic nucleoside analogue. While CP-4055 has similar mechanisms of action to cytarabine, it is, unlike cytarabine, independent of nucleoside transporters for cellular uptake.

Aims: Determination of efficacy and safety of CP-4055 in patients (pts) with haematologic malignancies receiving CP-4055 either as monotherapy or in combination with idarubicin.

Methods: The first patient was enrolled in May 2006. Pts received IV CP-4055 over 2 hours (2 hr IV) or 24 hours (CIV, Arm B) in a day 1–5 q3w schedule.

Results: Seventy-seven pts (46 male and 31 female) with a median age of 61 years (range 21– 92) were enrolled in the first phase I part. The majority of the pts presented with refractory/ relapsed AML and most pts had received two or more previous chemotherapeutic regimens. The recommended dose for CP-4055 monotherapy was determined to be 2000 mg/m²/d. Four pts had CR/CRp among 29 relapsed/refractory AML pts treated with this regimen The starting dose for CP-4055 in combination with idarubicin was 1150 mg/ m²/d CIV. Four pts (2 male, 2 female) have been enrolled. MTD has been determined at 1150 mg/m2/d and accrual is ongoing at 1000 mg/m2/d. DLTs were typhilitis and hand-foot-syndrome. In the phase II monotherapy part, accrual of patients with AML who have failed two prior lines of therapy is ongoing. The first evaluation for safety and futility will be prepared after 20 pts.

Summary/Conclusion: CP-4055 was well tolerated when administered both as 2–4 h IV and as CIV d1–5 q3w. The recommended dose for CP-4055 monotherapy was determined to be 2000 mg/m²/d in a d1–5 q3w schedule. The starting dose for CP-4055 in combination with idarubicin was 1150 mg/m²/d. MTD has been reached and accrual is ongoing at 1000 mg/m²/d.. The study continues.