BETHESDA, Md.—The National Cancer Institute has concluded that some of its lymphoma researchers failed to notify the Food and Drug Administration in a timely fashion about fungal infections that resulted in two deaths of patients in one of its research studies.
The lab in question has been studying the effects of a cocktail of drugs on an often-fatal and very rare lymphoma of the central nervous system. When two patients died from an infection of a commonly occurring fungus called aspergillus in 2015, the lab and the NCI were supposed to have reported those serious “adverse events” to the FDA within a matter of days, senior officials said.
The officials of the National Institutes of Health, of which the NCI is a part, said the patients’ immune systems were apparently suppressed by both their disease and the drug cocktail, and they thus became infected from a fungus that wouldn’t normally be dangerous. There were 18 total patients in the clinical study.
The NIH called the events “deeply troubling,” and said the delay in reporting to the FDA was “unacceptable.” But it said the 81% rate of shrinkage of tumors in patients was “the highest response rate of any targeted agent in this population of lymphoma patients.”
NIH Director Dr. Francis Collins said the first death from fungal infection occurred in 2015 and wasn’t considered especially noteworthy. But when a second death took place in late 2015, he said, the conclusion was that the drug cocktail—including steroids and a drug called ibrutinib—led to a likely extreme immune suppression that contributed to the deaths. Ibrutinib, sold as Imbruvica, was developed byJohnson & Johnson and Pharmacyclics LLC, a company AbbVie Inc. acquired in May 2015.
“Notification of a severe adverse event needs to be reported” within a matter of days to the FDA and an internal review board overseeing the study, Dr. Collins said. But that reporting didn’t occur until May 2016.
For the NIH, the case of the lymphoma trial is a new safety-related embarrassment. In May 2015, FDA inspectors found a contamination in two medicine vials in the pharmacy of the NIH Clinical Center. The NIH subsequently closed that pharmacy permanentlyafter the FDA made critical conclusions about the way the lab was run.
NIH officials said the latest case in the lymphoma study is unrelated to the contamination in the NIH pharmacy last year. In that case, medicine from that batch was given to six patients, but none of them developed signs of infection or illness.
Still, the combination of the cases caused relatively greater concern at the NIH, located in Bethesda, Md.
“Here is another example where we have documented a problem,” said Dr. Collins. He said he plans to ask all the institutes that make up the NIH to see if there have been cases of severe adverse events in clinical studies that weren’t reported to the FDA or other authorities in a timely fashion.
The lymphoma study’s principal investigator, Kieron M. Dunleavy, declined to comment.
The internationally renowned lymphoma program at NCI is run by Wyndham Wilson, who is Dr. Dunleavy’s supervisor. Dr. Wilson declined to comment.
William L. Dahut, a senior researcher and official of the NCI, said the lymphoma program “is one of our most spectacular programs.”
NIH officials said the lymphoma research ironically produced results that are considered “dramatically positive,” in the words of Dr. Collins. Eight of the 18 patients had a sustained remission, even though six of them had already not been helped by other treatments.
The director of the cancer institute, Douglas Lowy, presented the details of the matter Friday to the board of directors of the NIH’s hospital, where the research took place. The hospital, called the NIH Clinical Center, treats many of the patients from 17 of the research institutes at the NIH.
[Source:-The Wall Street journal]