Phase III Study for Acute Myeloid Leukemia Hailed as Landmark Trial

 

The American Journal of Managed Care (AJMC) published excerpts from a  presentation by Dr. Andrew Wei at the 61st American Society of Hematology (ASH) Annual Meeting. The article stated that CC-486 has emerged as the first treatment to demonstrate improvement when used as maintenance therapy for acute myeloid leukemia (AML) patients in their first remission.

AML is considered a blood disease although it usually begins to form in bone marrow and then moves into the blood.

Dr. Wei, who is associated with the Alfred Hospital in Melbourne, Australia, explained that previous studies of CC-486 in various Phase I trials demonstrated the drug’s efficacy in combating myeloid malignancies.

It is important to note that even patients whose disease had progressed when they were previously treated with azacitidine injections have now seen improvement.

Dr. Wei noted that since 1973 numerous studies have been conducted in an effort to improve the standard of care and overall survival in AML. Until the advent of CC-486, most attempts have failed.

CC-486 is an oral form of the hypomethylating agent azacitidine. Researchers have observed that azacitidine may re-activate genes called “tumor suppressors”. These genes were previously silenced by hypermethylation.

About the Phase III QUAZAR AML-001 Trial

The trial involved 472 subjects (median age of 68) who were within four months of having reached complete remission (CR). CR represents a normal count and no evidence of cancer. Other eligible patients were classified as CRi which means being in remission but having incomplete count recovery.

The patients were selected randomly and divided into two cohorts with half receiving CC-486 and the other cohort receiving a placebo. Both arms received treatment for fourteen days and were then allowed a fourteen day “rest period.” If either the count recovery or remission status was not maintained, the length of each cycle of treatment was increased to twenty-one days. The majority of patients received treatment through twelve cycles compared to six cycles for the placebo cohort. Some of the CC-486 patients received up to eighty cycles. Dr. Wei pointed out that this is a clear indication of the drug’s tolerability.

About Overall Survival (OS)

CC-486 extended overall survival (OS) by almost ten months in comparison to patients’ response in the placebo arm. At the end of the first year, forty-seven percent of the CC-486 patients were still in remission as compared to twenty-nine percent in the placebo cohort.

At the forty-one month follow-up, CC-486 patients showed an overall survival of almost twenty-five months. The overall survival period for the placebo cohort was approximately fifteen months.

About Adverse Events (AEs)

Thirty-four percent of the CC-486 patient cohort reported AEs versus twenty-five percent from the placebo group. No AEs were reported that might have resulted in the discontinuation of treatment. Infections accounted for seventeen percent of AEs in the CC-486 cohort versus eight percent in the placebo cohort.

CC-486’s safety profile is in line with injectable azacitidine. Both have demonstrated infrequent discontinuation of treatment resulting from AEs. No treatment related deaths were reported.

Dr. Wei stated that due to the positive nature of this “landmark trial” it is conceivable that CC-486 will be the new therapeutic standard for patients fifty-five and older who are in their first remission.

After announcing the QUAZAR results in September 2019, Celgene announced its plans to submit an application for FDA approval of CC-486 in 2020.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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