Cell Therapeutics Announces Presentation of Interim Results from Phase 2 Tosedostat Trial

Cell Therapeutics Announces Presentation of Interim Results from Phase 2 Tosedostat Trial in Older Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) at ASH Annual Meeting
-- Interim Results of Tosedostat in Combination with Chemotherapy or Hypomethylating Agents in First-line Demonstrate 54 Percent Complete Response Rate and 12-Month Median Survival --

SEATTLE, Dec. 10, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced promising interim results from an investigator-initiated Phase 2 clinical trial of tosedostat in combination with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Tosedostat is a first-in-class selective inhibitor of aminopeptidases, which are required by tumor cells to provide amino acids necessary for growth and tumor cell survival. Tosedostat is administered orally and has been previously shown to induce complete remissions as monotherapy in relapsed or refractory AML. Researchers presented the findings from this combination study today for the first time at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition held December 7–10 in New Orleans, La.

"Treatment outcomes for older patients with newly diagnosed AML remain poor," said John Pagel, M.D., Ph.D., Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center; Associate Professor, Medical Oncology Division, University of Washington School of Medicine; and Principal Investigator in the tosedostat first-line AML/MDS trial. "This is the first time that tosedostat has been given in a front-line setting in combination with low intensity therapy. The complete response rates and median survival observed in previously untreated older patients with AML is promising and appears to be worthy of further clinical investigation."  

The Phase 2 trial was designed to test the efficacy of tosedostat in combination with low intensity therapy for older patients with previously untreated AML or high-risk MDS not considered candidates for standard intensive therapy. This presentation reported on the results of 26 patients (median age was 69) enrolled in the first dose cohort. Patients were randomized to treatment with tosedostat in combination with either cytarabine or decitabine. Fourteen out of 26 (54 percent) patients in this cohort had either a complete response (CR; n=10, 39 percent) or complete response with incomplete blood count recovery (CRi; n=4, 15 percent). The percentage of complete responses was comparable between arms. Seven (50 percent) of the 14 CR/CRi were achieved in patients with poor-risk cytogenetic features. Importantly, 10 of the 26 patients subsequently went on to receive hematopoietic stem cell transplant. The study achieved its primary objective with 21 (82 percent) patients alive at four months. Median overall survival was encouraging at approximately 12 months for both study arms. Tosedostat combination therapy was well tolerated and predominantly administered as an outpatient therapy. The primary side effects of the combination therapy, the majority of which were associated with the cytarabine arm, included febrile neutropenia (50 percent), pulmonary infections (31 percent) and sepsis (19 percent).  Clinically significant non-hematological toxicities were uncommon and predominantly low grade.  

Abstract #3926:  A Phase II Study of Tosedostat (TST) in Combination with Either Cytarabine or Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS).  

The Phase 2 randomized, open-label trial enrolled patients 60 years of age or older with untreated AML or high-risk MDS to receive tosedostat 120 mg orally, once daily on days 1–21 with five days of either cytarabine 1 g/m2/day IV or decitabine 20 mg/m2/day IV delivered every 35 days. Patients received up to three cycles of therapy if they had at least stable disease following the initial course, and patients that achieved a CR/CRi were eligible to receive up to two additional cycles. The primary endpoint of the trial was to determine the CR rate and four-month survival. Secondary endpoints were to assess safety and tolerability of tosedostat with either cytarabine or decitabine, to estimate rates of disease-free survival and one-year overall survival. A total of 26 patients have been treated, with 13 receiving tosedostat/cytarabine and 13 receiving tosedostat/decitabine. Nineteen patients (73 percent) had AML and seven (27 percent) had high-risk MDS.  

The poster is available at www.celltherapeutics.com.

About Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Approximately 14,590 new cases of AML are expected to be diagnosed in the United States in 2013.1 As of January 2008, an estimated 30,993 people were living with (or were in remission from) AML.2 Although AML can occur at any age, adults aged 60 years and older are more likely to develop the disease than younger people. AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML may develop from the progression of other diseases, such as MDS, a blood cancer that also affects the bone marrow leading to a decrease in circulating red blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.

About Tosedostat

Tosedostat is an oral aminopeptidase inhibitor that has demonstrated significant anti-tumor responses in blood-related cancers and solid tumors in Phase 1–2 clinical trials. CTI has an exclusive marketing and co-development agreement with Chroma Therapeutics Ltd. for drug candidate tosedostat in North, Central and South America.

About Cell Therapeutics

Cell Therapeutics (NASDAQ and MTA: CTIC) is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable. CTI is headquartered in Seattle, WA. For additional information and to sign up for email alerts and get RSS feeds, please visit www.CellTherapeutics.com.

Forward-Looking Statements

This press release contains "forward-looking" statements that are made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the number of expected cases of AML expected to be diagnosed. Such statements are subject to risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results and the trading price of the Company's securities. Specifically, the risks and uncertainties that could affect our ability to address FDA requests or the development of tosedostat more generally include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with tosedostat in particular including, without limitation, the potential failure of tosedostat to prove safe and effective as determined by the FDA and/or the European Medicines Agency; determinations by regulatory, patent, and administrative governmental authorities; competitive factors; technological developments; costs of developing and producing tosedostat; the risk that the FDA may expand its information request or initiate a complete clinical hold or take other actions; 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, 10-Q and 8-K. The Company can give no assurances that any results or events projected or contemplated by its forward-looking statements will in fact occur and the Company cautions you not to place undue reliance on these statements. The Company undertakes no duty to update these forward-looking statements to reflect any future events, developments or otherwise.