FDA Places Clinical Hold on Leukemia Drug Trials

Multiple clinical trials of vadastuximab talirine have been placed on clinical hold by the FDA.

Seattle Genetics recently announced that the FDA has placed full or partial clinical holds on multiple trials of vadastuximab talirine (SGN-CD33A) in patients with acute myeloid leukemia.

The holds were placed on these trials due to concerns over the risk of hepatotoxicity in patients who were receiving the drug therapy, and who also received an allogeneic stem cell transplant before or after drug therapy, according to a press release from Seattle Genetics.

Thus far, there have been 6 patients with confirmed hepatotoxicity. Several of those patients developed veno-occlusive disease, which is an uncommon liver complication that results from a build-up of toxins in the body. These events led to deaths in 4 patients, which prompted the FDA to investigate.

Seattle Genetics plans to work closely with the FDA to determine whether there is a link between hepatotoxicity and vadastuximab talirine treatment. If a link is discovered, the pharmaceutical manufacturer will continue to partner with the FDA to determine proper protocol amendments to improve patient safety and continue the clinical trials, according to the press release.

To date, more than 300 patients have received treatment with vadastuximab talirine, which is an investigational drug that targets CD33 that is expressed highly in acute myeloid leukemia cells.

Vadastuximab talirine was previously granted orphan drug designation for the treatment of acute myeloid leukemia by the FDA and the European Commission.

A full clinical hold has been placed on the phase 1/2 clinical trial of vadastuximab talirine monotherapy in pre- and post-transplant patients with leukemia.

Two additional phase 1 clinical trials have been placed on partial clinical hold, which means no more patients may enroll, but the trial may continue if patients re-consent, according to the press release. No new studies will start until all clinical holds are removed.

Both of these studies are investigating the drug as a monotherapy, with a subset of older patients undergoing combination treatment with hypomethylating agents, and newly diagnosed patients undergoing treatment with vadastuximab talirine in combination with 7+3 chemotherapy.

However, other ongoing trials, such as the phase 3 CASCADE trial in older patients, and the phase 1/2 clinical trial in myelodysplastic syndrome, are continuing to enroll patients, the press release concluded.