Phase II Study of Zevalin Consolidation Following Fludarabine andMitoxantrone Chemotherapy Results in 100 Percent Complete RemissionRate and 89 Percent Three-Year Progression Free Survival inPatients with Previously Untreated Non-Follicular Indolent LymphomaPhase II Investigational Trial Published in CANCER: the Journal of the American Cancer Society
SEATTLE, January 22, 2008 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) announced today that results of a phase II clinical study, published in the journal CANCER demonstrate that 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.
The study results are reported in the current issue of CANCER at http://www3.interscience.wiley.com/journal/104532863/issue
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"
Zevalin(R) (Ibritumomab Tiuxetan) is a form of cancer therapy called radioimmunotherapy and is indicated for the treatment of patients with relapsed or refractory low-grade or follicular B-cell NHL, including patients with Rituximab-refractory NHL. It was approved by the FDA in February of 2002 as the first radioimmunotherapeutic agent for the treatment of NHL.
Deaths associated with an infusion reaction symptom complex have occurred within 24 hours of rituximab infusions. Yttrium-90 Zevalin administration results in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions have been reported. The most serious adverse reactions of the Zevalin therapeutic regimen were primarily hematologic, including neutropenia, thrombocytopenia, and anemia. Infusion-related toxicities were associated with pre-administration of rituximab. The risk of hematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Myelodysplasia or acute myelogenous leukemia was observed in 2 percent of patients (8 to 34 months after treatment). Zevalin should only be used by health care professionals qualified by training and experience in the safe use of radionuclides.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.
This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of Zevalininclude risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with Zevalin in particular including, without limitation, the potential failure of Zevalin to prove safe and effective as consolidation therapy following treatment with a regimen of fludarabine and mitoxantrone for treatment of non-Hodgkin's lymphoma, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling Zevalin, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Posted: January 2008