Clinical Trial Shows Progression Free Survival In Patients With Non-Follicular Indolent
Cell Therapeutics announced results of a phase II clinical study: the addition of radioimmunotherapy (RIT) to chemotherapy for previously untreated patients with non-follicular indolent non-Hodgkin's lymphoma (NHL) was both well tolerated and effective, producing a 100 percent complete remission at end of treatment with an estimated 89 percent of patients remaining in remission at three years.
The study, conducted at the Institute of Hematology and Medical Oncology at University of Bologna, Italy, investigated the use of a single dose of Zevalin(R) (Ibritumomab Tiuxetan) as consolidation therapy following treatment with a regimen of fludarabine and mitoxantrone (FM chemotherapy) among 26 patients with newly diagnosed non-follicular indolent NHL. Non-follicular lymphomas are also referred to as intermediate grade compared to the low grade follicular or high grade diffuse B cell variety. FM chemotherapy resulted in 50 percent of patients achieving a complete remission (CR) and 30 percent achieving a partial remission (PR). Of the 20 patients (13 with CR and 7 with PR) who were evaluable for Zevalin consolidation, 100 percent obtained a CR at the end of treatment. With a median follow up of 20 months, the estimated three-year progression free survival (PFS) was 89.5 percent. The most common greater than or equal to grade 3 toxicities included neutropenia (11 patients) and thrombocytopenia (16 patients).
"This single arm, non-randomized phase II trial provides additional insights into the potential utility of RIT in intermediate grade NHL, a subtype where CRs are infrequent with rituximab therapy," noted Jack W. Singer, M.D., Chief Medical Officer of CTI.
Between February 2005 and June 2006 26 eligible patients with previously untreated, indolent, nonfollicular NHL (10 marginal zone, 8 lymphocytoplasmic, and 8 small lymphocytic) were treated using a novel regimen that consisted of 6 cycles of fludarabine/mitoxantrone (FM) chemotherapy followed 6 to 10 weeks later by yttrium-90(90Y) ibritumomab tiuxetan (Zevalin(R)). After chemotherapy the overall response rate was 80.5% and included 50% CR and 30.5% PR. Of the 20 patients (13CR/7PR) who were evaluable (at least a PR with normal platelet counts and bone marrow infiltration <25%) for subsequent Zevalin, 100% obtained a CR at the end of treatment. With a median follow up of 20 months, the estimated three-year progression free survival (PFS) was 89.5 percent. The FM treatment was well-tolerated; there were no treatment-related deaths. Reversible hematologic toxicities included neutropenia grade 4 in 5 patients and grade 3 in 13 patients. Only 1 patient developed febrile neutropenia.
Following Zevalin administration grade 3-4 thrombocytopenia occurred in 16 of 20 patients with grade 3-4 neutropenia reported in 11 of 20 patients. Four patients received GCSF and 3 patients received platelet transfusions. Only 1 patient experience febrile neutropenia. The authors concluded "In this study we established the feasibility, tolerability and efficacy of sequential treatement with 6 cycles of FM chemotherapy followed by 90Y ibritumomab tiuxetan as front line therapy for patients with untreated, indolent, nonfollicular NHL. To our knowledge the data represent the first demonstration in the literature of the real role of 90Y ibritumomab tiuxetan in the treatment of indolent nonfollicular NHL. Because this novel sequential treatment appears to be promising compared with results reported for CHOP and CVP- containing regimens plus rituximab, we believe the current phase II trial represents an important first step and positive new angle in therapy to combat indolent, nonfollicular NHL"