The Phase 3 trial testing Rafael Pharmaceuticals‘ CPI-613 (devimistat) as a treatment for relapsed or refractory acute myeloid leukemia (AML) has enrolled more than half of the participants needed for its first interim analysis, the company has announced.

The pivotal ARMADA 2000 trial (NCT03504410) is investigating whether CPI-613 increases the sensitivity of cancer cells to chemotherapy in older AML patients, potentially enabling lower chemotherapy doses and fewer adverse side effects in these patients.

While many clinical trials have been impacted by the ongoing pandemic, Rafael expanded safety protocols, enabling its trials to continue enrolling and treating participants. ARMADA 2000 is enrolling participants at more than 60 clinical sites around the world, including in the U.S., Canada, Australia, Europe, India, and South Korea. For more information on contacts and locations, click here.

“Actively and safely enrolling patients and reaching the midpoint to the first interim analysis is an achievement worth noting, especially given the challenges for clinical trial enrollment across the globe due to the coronavirus pandemic,” Jorge Cortes, MD, the trial’s lead investigator and director of the Georgia Cancer Center at Augusta University, said in a press release.

“Relapsed or refractory AML remains a significant challenge for older patients, so it is encouraging to see enrollment continue to grow,” added Cortes, who developed the study’s rationale and design.

CPI-613 is a first-in-class molecule that blocks enzymes involved in cancer cell metabolism. These enzymes are located in the mitochondria, also known as the cell’s powerhouses because their function is to convert nutrients into energy for normal cell functioning.

But in cancer cells, changes in the regulation of these proteins cause the mitochondria to shift their function and convert nutrients into the building blocks of the next cancer cell. By targeting these proteins, CPI-613 is thought to inhibit mitochondria in cancer cells, impairing their ability to survive chemotherapy.

This synergy with chemotherapy suggests that CPI-613 may be used to lower the chemotherapy doses currently used in clinical practice, and thereby reduce adverse events experienced by patients.

ARMADA 2000 is investigating a combination of CPI-613 plus high-dose cytarabine and mitoxantrone versus high-dose cytarabine and mitoxantrone in people, ages 50 and older, with relapsed or refractory AML.

After working closely with the U.S. Food and Drug Administration (FDA) because of enrollment challenges, Rafael recently amended the protocol to include control subgroups receiving two other chemotherapy combinations: one containing cytarabine, mitoxantrone, and etoposide; and another consisting of cytarabine, fludarabine, and filgrastim.

The trial’s main goal was to determine whether the CPI-613 combination increased the proportion of patients attaining a complete response (or the complete disappearance of all cancer signs), compared with the chemotherapy regimens.

Secondary measures include overall survival and complete response rate, with or without full recovery of blood cell counts. The trial aims to recruit 500 participants, and top-line findings are expected by October 2022.

“This enrollment milestone provides hope to these patients, as we work to deliver more effective treatments to patient populations that have few viable options,” said Sanjeev Luther, president and CEO of Rafael Pharmaceuticals. “We are deeply appreciative of all of our principal investigators, patients and caregivers for their continued support of this trial.”

In addition to AML, Rafael is testing CPI-613 in multiple trials across a range of cancer indications. These include AVENGER 500 (NCT03504423), a pivotal Phase 3 trial testing the agent in metastatic pancreatic cancer.

The FDA has named CPI-613 an orphan drug for the treatment of AML, pancreatic cancer, myelodysplastic syndrome, peripheral T-cell lymphoma, and Burkitt lymphoma. The compound has also received orphan drug designation for AML and pancreatic cancer from the European Medicines Agency.