Leukemia & Lymphoma publishes CTI's CPOP phase I/II trial results against NHL

Cell Therapeutics, Inc. ("CTI") (NASDAQ and MTA: CTIC) announced today that the April 2011 edition of the peer reviewed journal, Leukemia & Lymphoma (April 2011; 52(4): 620–628) published results of a phase I/II clinical trial evaluating the effect of cyclophosphamide, pixantrone, vincristine, and prednisone ("CPOP") in treating patients with aggressive non-Hodgkin's lymphoma ("NHL") who relapsed following initial therapy with cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone ("CHOP").  In the CPOP regimen, pixantrone substitutes for doxorubicin (H) in the CHOP regimen.  Peter Borchmann, M.D., of the University Hospital of Cologne, led the study.  CPOP produced high rates of complete remissions ("CR") and overall response rate ("ORR").  In some patients, these remissions were highly durable despite patients having relapsed after receiving CHOP and other multi-agent therapies.  

The study enrolled 35 patients in the phase I portion of the trial and 30 patients in the phase II portion of the trial. A major tumor response was reported for 80% and 73% of patients in phase I and II respectively, with 57% and 47% of the patients achieving a complete or unconfirmed CR. Median overall survival in the phase II portion of the trial was 17.9 months with four patients achieving notable long-term disease-free survival ranging from 55 to 77 months, despite in some cases having failed multiple prior regimens including stem cell transplantation. High response rates were also observed in the 43% of patients who had received prior rituximab as part of their front-line regimen (CHOP-R), with an ORR rate of 77% and CR rate of 54%. Myelosuppression was the most common toxicity. Side effects (grade 3/4) in phase I of the trial included febrile neutropenia (11%), grade 3/4 infections (3%), and cardiac failure (6%). In phase II of the trial, side effects (grade 3/4) included febrile neutropenia (20%), and cardiac failure (3%).

"Although there are a number of treatment regimens that have been studied as salvage therapies in patients with relapsed aggressive NHL, few have demonstrated a high proportion of complete responses and many of the remissions achieved are of relatively short duration," said Jack W. Singer, M.D. Chief Medical Officer at CTI. "Patients who have completed a course of CHOP therapy are unable to be retreated with the same regimen due to the potential for severe heart toxicity when the lifetime limit of doxorubicin is exceeded.  Pixantrone has substantially less cardiotoxicity than doxorubicin in animal models and was found to be adequately tolerated in patients treated with prior doxorubicin in phase I trials.  The present study suggests that use of pixantrone with CPOP not only offers a high response rate, but in some patients these responses had impressive durability.  Four patients in the study had unmaintained remissions of between 4+ and 6+ years duration following CPOP, which is highly unusual in the setting of treating relapsed disease. The opportunity to re-challenge patients with a CHOP-like regimen, using pixantrone instead of doxorubicin after relapse from initial therapy with CHOP indicates that pixantrone-based regimens may represent a new approach to managing relapsed aggressive NHL. A Phase III clinical trial with pixantrone in this setting has recently been initiated, the PIX-R TRIAL™."