Up to 30% of patients newly diagnosed with acute myeloid leukemia (AML) have an FLT3 gene mutation, which is associated with a high risk of relapse and a very poor prognosis. To complicate matters, often they are ineligible for intensive induction chemotherapy due to advanced age or overall poor health.

But previous studies have shown that FLT3 inhibitors can extend survival in these patients, especially when administered in combination with other therapies. A clinical trial underway at Roswell Park Comprehensive Cancer Center is evaluating that strategy with the FLT3 inhibitor gilteritinib (brand name Xospata), combining it with the BCL-2 inhibitor venetoclax (brand names Venclexta, Venclyxto) and the low-dose chemotherapy drug azacitidine (brand names Vidaza, Onureg).

“We are one of few centers participating in this trial, which hopes to address an unmet need in our elderly patients,” says Eunice Wang, MD, Chief of the Leukemia/Benign Hematology Service and Leukemia Clinical Disease Team Leader at Roswell Park. Dr. Wang serves as site principal investigator for “A Phase 1/2, Multicenter, Open-Label, Randomized Dose-Ranging and -Expansion Study of the Combination of Gilteritinib, Venetoclax and Azacitidine in Patients with Newly Diagnosed FLT3 Mutated Acute Myeloid Leukemia (AML) Not Eligible for Intensive Induction Chemotherapy” (NTC05520567), which aims to enroll 70 patients.

“The VICEROY trial is the first multicenter trial to investigate the appropriate dosage and preliminary efficacy of a triplet approach for older, unfit patients with newly diagnosed FLT3-mutant AML,” explains Dr. Wang. “While standard therapy with venetoclax/azacitidine and clinical trial therapy with the FLT inhibitor gilteritinib plus azacitidine led to improved clinical responses, these did not result in improved overall outcomes for these patients over azacitidine alone. Therefore, administering all three drugs together might be the solution.”

In 2018 the FDA approved the use of azacitidine with venetoclax in older AML patients, and studies have demonstrated that the combination can extend survival. Gilteritinib was FDA-approved the same year for the treatment of relapsed or refractory FLT3-mutant AML. Two of the three drugs (venetoclax, gilteritinib) are given orally, and azacitidine as a subcutaneous injection.

“If it shows promise, this triple-drug regimen has the potential to be developed into the new standard of care, if drug dosage, duration and toxicity can be optimized for these more-frail individuals,” says Dr. Wang.