Phase 3 Trial Underway to Assess Gilteritinib as Maintenance Therapy in Certain AML Patients

Phase 3 Trial Underway to Assess Gilteritinib as Maintenance Therapy in Certain AML Patients

The first participant has  begun treatment in a new Phase 3 clinical trial assessing Astellas Pharma‘s gilteritinib as a maintenance therapy for certain acute myeloid leukemia (AML) patients who are in remission following a stem cell transplant.

The multicenter, randomized MORPHO study (NCT02997202) is recruiting participants with AML who are positive for a genetic abnormality known as FLT3 internal tandem duplication (FLT3-ITD).

“We know that FLT3+ AML patients face potentially worse outcomes than those with other mutations, and while some patients may experience remission following a stem cell transplant, many unfortunately relapse,” Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and investigator in the MORPHO trial, said in a press release. “Given this reality, it is exciting to study gilteritinib in patients following a stem cell transplant.”

Nearly one in every three persons with AML carry genetic mutations that permanently activate the FLT3 cell surface receptor, which helps malignant cells survive.

Gilteritinib, formerly known as ASP2215, has been shown to inhibit FLT3-ITD as well as another common FLT3 mutation, called FLT3 tyrosine kinase domain. In addition, the drug also blocks AXL, which has been associated with treatment resistance in cancer.

Currently, Astellas is testing gilteritinib in multiple Phase 3 trials for several AML populations, which include ADMIRAL trial (NCT02421939) for relapsed or refractory AML patients harboring FLT3 tyrosine kinase domain (TKD) mutations (FLT3-TKD).

The new Phase 3 trial is assessing the safety and efficacy of gilteritinib versus a placebo as a maintenance therapy, given for a period of two years after stem cell transplant to FLT3-ITD-positive, AML patients who are in remission.

The trial is being conducted in collaboration with the Blood and Marrow Transplant Clinical Trials Network, and expects to enroll 346 participants in centers across North America, Japan, Republic of Korea, Spain, and Poland.

Participants will be randomized to receive either gilteritinib (120 mg) once a day, or a placebo, starting 30 to 90 days after stem cell transplant.

The researchers’ main objective is to determine if gilteritinib can delay leukemia relapse or death, measured as relapse-free survival. They will also determine the safety and tolerability of gilteritinib, as well as other efficacy measurements such as overall event-free survival, among others.

“The initiation of the MORPHO trial is another significant milestone for Astellas and for patients as therapeutic options can be very limited for this FLT3+ AML population,” said Steven Benner, MD, senior vice president and global therapeutic area head of oncology development at Astellas. “We are committed to patients with FLT3+ AML and currently have underway four Phase 3 trials to explore the potential benefit of gilteritinib for patients suffering from such an aggressive form of blood cancer characterized by both genetic and resistance mutations.”

In July 2017, the U.S. Food and Drug Administration granted orphan status to gilteritinib for the treatment of AML.

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