Phase II study of investigational regimen demonstrates important role of radioimmunotherapy in converting partial remissions to complete remissions
and inducing a high rate of molecular remissions
SEATTLE, March 17 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; MTA) today announced that patients with previously untreated follicular non-Hodgkin's lymphoma (NHL) treated with fludarabine and mitoxantrone, followed by administration of Zevalin(R) (Ibritumomab Tiuxetan), achieved 96 percent complete remission (CR), an estimated three-year progression-free survival (PFS) rate of 76 percent, and a 100 percent estimated three-year overall survival (OS) rate. The side effects were generally mild without any signs of cumulative toxicity, and hematological side effects were moderate. Results of the study were reported in the online edition of The Lancet (Lancet Oncology, DOI:10.1016/S1470-2045(08)70039-1). CTI acquired the U.S. rights to Zevalin in December, 2007.
The objective of the study was to determine the tolerability and efficacy of Zevalin consolidation following sequential fludarabine and mitoxantrone therapy without rituximab in first-line treatment of follicular NHL.
"This study underscores the potential use of radioimmunotherapy with Zevalin to convert the majority of partial remissions to complete remissions and to induce molecular remissions after conventional chemotherapy, both of which correlate with durable progression-free survival rates," noted Jack W. Singer, M.D., Chief Medical Officer at CTI.
A total of 61 patients with advanced (stage III-IV) follicular NHL were treated with six cycles of fludarabine and mitoxantrone chemotherapy; 57 patients (43 with CR and 14 with PR) were subsequently treated with Zevalin therapy. Consolidation with Zevalin converted 12 of 14 partial remissions (86 percent) to complete remissions for a complete response rate of 96 percent. With a median follow-up of 30 months, estimated three-year progression-free survival (PFS) was 76 percent and estimated three-year overall survival 100 percent. Twenty two percent of patients tested (5 of 23) achieved a molecular remission following chemotherapy. Zevalin consolidation induced a molecular remission in 14 of 18 patients (78 percent) tested who did not achieve a molecular remission after fludarabine-mitoxantrone therapy. Grade 3/4 thrombocytopenia, neutropenia, and anemia occurred in 63 percent (36 of 57), 53 percent (30 of 57), and 23 percent (13 of 57), respectively. Febrile neutropenia occurred in 9 percent (5 of 57) of patients. Patients who relapsed were treated with CHOP + rituximab as salvage therapy and all tolerated six cycles of therapy indicating that treatment with Zevalin did not preclude the ability to administer an aggressive salvage regimen.
Details of the Study
The phase II trial, reported by P.L. Zinzani et. al. from the Institute of Hematology and Medical Oncology at the University of Bologna in Bologna Italy, was a prospective, single-arm, open-label, multi-center, non-randomized trial, known as FLUMIZ (FLUdarabine, MItoxantrone, Zevalin). The trial was conducted at 13 Italian institutions to evaluate the efficacy and safety of this regimen as first-line therapy in untreated patients with follicular non-Hodgkin's lymphoma. Patients with stage III or IV untreated indolent follicular NHL were treated with oral fludarabine and intravenous mitoxantrone every 28 days for six cycles. Patients who had at least a partial response with adequate platelet counts (>100x10^9/L) and granulocyte counts (1.5x10^9/L), and bone marrow tumor infiltration of less than 25 percent four to six weeks after completion of the sixth cycle of chemotherapy were deemed eligible for consolidation treatment six to ten weeks after the sixth cycle with one course of Zevalin. Primary endpoints were complete response and hematological toxic effects and secondary endpoints were overall survival and progression-free survival.
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.
Rare 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.
Patients and healthcare professionals can visit http://www.zevalin.com for more information.
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. For additional information, please visit http://www.cticseattle.com.
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 Zevalin include 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 in further studies in combination with fludarabine and
mitoxantrone for first-line treatment of untreated patients with follicular
NHL or to be developed further in this combination for this indication,
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.
|SOURCE Cell Therapeutics, Inc.|
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