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Phase 2 study of MLN8237: Investigational aurora A kinase (aak) inhibitor in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS)

Date:
December 7, 2010
Source:
John Theurer Cancer Center
Summary:
Aurora A kinase is essential for cell division (mitotic progression) and is amplified or overexpressed in AML and other blood cancers. An investigational drug, MLN8237 is an orally available, potent, and selective AAK inhibitor. It has shown preclinical activity against leukemia, lymphoma, and myeloma, and clinical activity against treatment-resistant cancers in early-stage human trials.

Dr. Stuart Goldberg, Chief, Leukemia, John Theurer Cancer Center led this open-label, multicenter, phase 2 trial of MLN8237 in patients with advanced AML or intermediate/high-risk MDS. AAK is essential for cell division (mitotic progression) and is amplified or overexpressed in AML and other blood cancers. An investigational drug, MLN8237 is an orally available, potent, and selective AAK inhibitor. It has shown preclinical activity against leukemia, lymphoma, and myeloma, and clinical activity against treatment-resistant cancers in early-stage human trials.

Fifty-seven patients with a median age of 72 years old (range 46-85) were enrolled in the current study. Patients received 21-day cycles of MLN8237 (50 mg) for seven days followed by 14 days rest until disease progression or unacceptable toxicity. Forty-six (81%) patients had AML, of whom 21 (37%) had secondary leukemia, while 11 (19%) patients had MDS.

Dr. Goldberg and colleagues concluded MLN8237 has anti-leukemia activity with a 13% response rate (all AML) with advanced, mainly pre-treated disease.

"We found that patients for with rapidly progressive disease, improved outcomes require strategies to enhance both disease control and risk management in early cycles, allowing time needed to achieve clinical benefit from AAK inhibition," said Dr. Goldberg. "Our results support further clinical studies of MLN8237 in heme-lymphatic malignancies and solid tumors."

The Eastern Cooperative Oncology Group, one of the largest clinical cancer research organizations in the United States, previously reported superior one and two-year survival for newly diagnosed symptomatic multiple myeloma patients initially treated with lenalidomide plus low-dose dexamethasone, versus those treated with lenalidomide plus high-dose dexamethasone. As a result of this analysis, lenalidomide plus low-dose dexamethasone is now considered the standard of care.

In this multicenter trial, lead author David Vesole, MD, PhD, FACP, Co- Chief and Director of Research, Multiple Myeloma, John Theurer Cancer Center and colleagues evaluated the impact of age on dexamethasone dose intensity and overall survival.

The study randomly assigned 445 to patients to LD (233 patients) or Ld (222 patients) treatment groups and analyzed data for all enrolled patients ("intent-to-treat" analysis) for overall survival. Patients in the high-dose group did not have better overall survival at any age, while the higher dose was more toxic.

"Our findings confirmed that as originally reported, low-dose dexamethasone should be the standard of care for all newly diagnosed multiple myeloma patients regardless of age," said Dr. Vesole.

This research was presented at the annual meeting of the American Society of Hematology (ASH) taking place December 4-7, 2010 in Orlando, Florida.


Story Source:

The above story is based on materials provided by John Theurer Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

John Theurer Cancer Center. "Phase 2 study of MLN8237: Investigational aurora A kinase (aak) inhibitor in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS)." ScienceDaily. ScienceDaily, 7 December 2010. <www.sciencedaily.com/releases/2010/12/101207130341.htm>.
John Theurer Cancer Center. (2010, December 7). Phase 2 study of MLN8237: Investigational aurora A kinase (aak) inhibitor in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2010/12/101207130341.htm
John Theurer Cancer Center. "Phase 2 study of MLN8237: Investigational aurora A kinase (aak) inhibitor in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS)." ScienceDaily. www.sciencedaily.com/releases/2010/12/101207130341.htm (accessed April 18, 2014).

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