Leukemia doctor creates a clinical trial for patients ineligible for clinic trials

What if you or a loved one had cancer but were denied access to a research study testing a potentially beneficial treatment?
This scenario can be a frustrating reality for cancer patients who, because of health conditions or other reasons, aren’t allowed to participate in clinical trials.

“Most cancer clinical studies exclude patients with co-morbidities, active or recent malignancies, organ dysfunction or poor performance status,” says Guillermo Garcia-Manero, M.D., a professor of Leukemia. “How these criteria protect patients is unclear. Although some are based on clinical reasoning, it seems these criteria are in place more to protect the drug or intervention being studied than the patient.”

Garcia-Manero led a novel study of a combination of the chemotherapy drugs azacitidine (AZA) and vorinostat that revealed some acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients who typically couldn’t be considered for clinical trials because of other illnesses or poor performance status – a measure of disease progression
– responded well and were safely treated in the protocol setting.

Initially, 30 patients age 17 and older who hadn’t been treated for either disease previously and who had poor performance, poor renal or hepatic function or any other active systemic disorder such as another cancer were enrolled in the study. Sixty-day survival was 83% with low-grade gastrointestinal side effects reported.

The study was expanded to include an additional 79 patients. Sixty-day survival for the second group was 79% with a median overall survival of 7.6 months. The average event-free survival was 4.5 months. Again, only low-grade gastrointestinal side effects were observed.

The study was designed with “stopping rules” that included monitoring of side effects and complete response rates.

Patients were immediately placed on another therapy if their assigned therapy didn’t indicate there would be a complete response within a 60-day period. To define the minimum expected survival and response rates that would trigger the
stopping rules, researchers relied on prior data of 181 patients previously treated at MD Anderson.

The study points to the need for further evaluation of standard exclusion criteria, which could increase the pool of patients likely to benefit from therapy, and lead to larger clinical trials in the future specifically treating patients with AML and MDS.

“Participation in clinical trials is fundamental for the development of new therapeutic interventions,” says research team member Guillermo Montalban-Bravo, M.D., a fellow in Leukemia. “Despite this need, only 3 to 5 percent of patients with cancer treated in the U.S. currently are enrolled in clinical trials.”