Tosedostat OPAL Study in Acute Myeloid Leukemia Published in Lancet Oncology

SEATTLE, March 4, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) and Chroma Therapeutics Ltd. announced today that Lancet Oncology has published results from the OPAL Phase 2 study of tosedostat in elderly patients with relapsed or refractory acute myeloid leukemia (AML). Tosedostat is an oral aminopeptidase inhibitor which has been shown to deprive tumor cells of the amino acid building blocks they need to make proteins necessary for tumor cell survival. The lead author was Dr. Jorge Cortes, Professor of Medicine and Internist, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, Texas.

The trial showed that once-daily oral tosedostat resulted in a disease control rate of 51%. Subset analyses suggested the greatest benefit occurred in the difficult-to-treat patients with prior myelodysplastic syndrome (MDS) or those that had received prior hypomethylating therapy (HMA). Adverse events were mild, predictable and manageable.

About the OPAL Study
This Phase 2 multicenter, randomized study evaluated the safety and efficacy of two dose regimens of tosedostat to determine an appropriate regimen for future clinical studies. The study enrolled 73 patients randomized to two treatment arms:  tosedostat 120 mg once daily for six months or 240 mg once daily for two months followed by 120 mg once daily for four months. The median age of the patients was 72 years old. Prior primary induction therapy for AML included 58% of the patients treated with Ara-C plus anthracycline or other Ara-C regimens, 36% of the patients treated with HMAs and 7% of the patients treated with other regimens. Fifty-two percent had been refractory to primary induction therapy. As previously presented at the 53rd American Society of Hematology Annual Meeting, results included:

  • Overall response rate (ORR) of 22% (16/73), with 10% (7/73) achieving a complete response (CR) and 29% (21/73) of patients achieving stable disease (SD) for a disease control rate of 51%.
  • High response rates were observed in patients who previously received HMAs or initially were diagnosed with MDS, with an ORR of 38% (10/26) and 37% (7/19), respectively.
  • Median overall survival (OS) for patients achieving a CR was 322 days; partial response (PR) 195 days; and SD 162 days.
  • Adverse events were similar between dosing groups. Tosedostat was generally well-tolerated, with the majority of adverse events of grade 1 and 2. The most common treatment-related serious adverse event was febrile neutropenia reported in 29% of patients. 

"There are limited therapeutic options available for elderly patients who, after failing hypomethylating therapy, experience AML progression from MDS," said Dr. Cortes. "The novel mechanism of action and observed response rate in this completed Phase 2 study suggests that tosedostat could address this unmet medical need. We are currently conducting a Phase 2 study investigating the combination of tosedostat with azacytidine - an HMA, or low-dose cytarabine, a standard leukemia therapy in patients with relapsed or refractory AML and MDS - to determine if tosedostat would be safe and more effective when used in combination with these agents." 

The publication by Dr. Cortes, et al. titled "Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukemia (OPAL): a randomized open-label phase 2 study," is available at http://www.thelancet.com/journals/lanonc/issue/current.

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

About 13,780 new cases of AML were expected to be diagnosed in the United States in 2012.1 As of January 2008 an estimated 30,993 people were living with (or were in remission from) AML.  Although AML can occur at any age, adults aged 60 years and older are more likely to develop the disease than younger people.2 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 myelodysplastic syndrome (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 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 exclusive marketing and co-development rights to Chroma Therapeutics Ltd.'s drug candidate tosedostat in North, Central and South America.

About CTI

Cell Therapeutics, Inc. (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.

About Chroma Therapeutics

Chroma Therapeutics Limited, based in Oxford (UK), is a drug development company focused in the fields of oncology and inflammatory disorders. Chroma is building a broad pipeline of first- or best-in-class treatments utilising its expertise in chromatin biology and its novel intracellular accumulation technologies, which include the ability to selectively target drugs to macrophages. Chroma is backed by a number of leading specialist investors, including Abingworth, Essex Woodlands, Gilde, Phase4 and The Wellcome Trust. More information about Chroma can be found at www.chromatherapeutics.com.

References:

1. American Cancer Society, Cancer Facts & Figures 2012. Available at http://tinyurl.com/8kylgc7. Accessed February 2013.
2. The Leukemia and Lymphoma Society, Acute Myeloid Leukemia, Rev. 2011. Available at http://tinyurl.com/d72ycja. Accessed February 2013.

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 and the trading price of CTI's securities. Specifically, the risks and uncertainties that could affect the development of tosedostat 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 for the treatment of AML, MDS, multiple myeloma, blood related cancers and solid tumors as determined by the U.S. Food and Drug Administration and/or the European Medicines Agency; that tosedostat may not be more effective when used in combination with azacytidine; that CTI cannot predict or guarantee the pace or geography of enrollment of its clinical trials;  determinations by regulatory, patent, and administrative governmental authorities; competitive factors; technological developments; costs of developing and producing tosedostat; and the risk factors listed or described from time to time in CTI's filings with the Securities and Exchange Commission, including, without limitation, CTI's most recent filings on Forms 10-K, 10-Q and 8-K. 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.

Contacts at CTI:

Monique Greer
+1 206.272.4343
mgreer@ctiseattle.com

Ed Bell
+1 206.282.7100
invest@ctiseattle.com

Contact at Chroma Therapeutics:

Richard Bungay
+44 (0)1235 829137
rbungay@chromatherapeutics.com

SOURCE Cell Therapeutics, Inc.

Web Site: http://www.celltherapeutics.com

Posted: March 2013

View comments

Hide
(web3)