A phase I/IIa clinical trial of CLAOP21 and CLAOP14 in patients with high-grade non-Hodgkin's lymphoma and cardiac risk factors

Abstract

6708 Background: CHOP is the standard combination chemotherapy for high-grade Non-Hodgkin's-lymphoma (NHL). Pegliposomal doxorubicin in comparison to free doxorubicin has minimal cardiotoxicity. We performed a phase I/II study of a modified CHOP regimen including pegliposomal doxorubicin, termed CLAOP, in patients with high-grade NHL and cardiac risk factors. Methods: A three-weekly (CLAOP21) and a bi-weekly (CLAOP14) regimen were explored: CLAOP21 with 20mg/m2 of pegliposomal doxorubicin every 21 days, and a dose-dense CLAOP14 regimen every 14 days with escalating doses of pegliposomal doxorubicin supported by G-CSF. Results: 113 treatment cycles were administered to 22 patients. In the initial 12 patients CLAOP21/20mg/m2 was well tolerated with a degree of hematotoxicity similar to that reported with regular CHOP. The dose-dense CLAOP14/20mg/m2 was not associated with dose-limiting hematotoxicity, but three febrile episodes occurred in 27 treatment cycles. CLAOP14/25mg/m2 was associated with dose-limiting hematotoxicity and palmar plantar erythema. Grade III leucopenia and febrile infections developed in 3 of 5 patients, and PPE grade III in 2 of 5 patients, respectively. Both, the 3-weekly and the 2-weekly regimens were active with an overall response rate of 60%. Cardiotoxicity attributable to doxorubicin was not observed in any patient. Conclusions: The recommended dose of pegliposomal doxorubicin in the CLAOP regimen for Phase II/III testing is 20mg/m2. This regimen can be administered to lymphoma patients with concomitant cardiovascular disease without apparent cardiotoxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough