Clinical Trials Investigate Novel Approaches for Treating AML

Two clinical trials being conducted at Baptist Health Miami Cancer Institute are using novel therapeutic approaches to treat patients with acute myeloid leukemia (AML). AML, a form of blood cancer, can be aggressive or classified at high-risk based on the detection of certain molecular structures. Patients with high-risk AML are at risk of developing disease recurrence, calling for the need for novel and innovative approaches to improve their outcomes.

Patients in the two trials undergo initial chemotherapy followed by an allogeneic (donor-derived) stem cell transplantation. The first trial, which began enrolling patients recently, uses CRISPR technology to down-regulate a donor’s gene. The second trial uses CAR T-cells ― a form of immunotherapy ― generated from the stem cell donor to specifically target the leukemic cell population at the time of disease recurrence following the stem cell transplant.

Guenther Koehne, M.D., Ph.D., deputy director of Miami Cancer Institute and chief of blood and marrow transplantation and hematologic oncology

“We have made significant progress in the treatment of leukemia in the last decade,” said Guenther Koehne, M.D., Ph.D., deputy director of Miami Cancer Institute, chief of blood and marrow transplantation and hematologic oncology and co-investigator of the studies. “The results of this latest research are enabling us to deliver more sophisticated and customized care and to treat many individuals who remain at risk of leukemia recurrence.”

One of the most common leukemias in adults, AML is diagnosed in approximately 20,000 patients in the U.S. each year. About half of those who receive a hematopoietic cell transplant go on to relapse and their prognosis is poor. Dr. Koehne and his team have developed a unique technique to manipulate donor cells in the lab to reduce the risk of graft-versus-host disease (GVHD), a serious, sometimes life-threatening complication of transplantation.

At the Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies in March, Dr. Koehne, the symposium’s director, shared the latest updates from the principles on CAR T-cell therapies in AML patients, as well as the early results on the CRISPR technology-based clinical trial, “Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML” (NCT04849910).

“Through CRISPR, which is gene-editing technology, we remove CD33 from healthy cells so that the leukemia cell is now the only cell producing CD33,” Dr. Koehne said. “The resulting transplant product, known as tremtelectogene empogeditemcel, or trem-cel, protects the healthy cells and allows drugs to better target and kill the cancer cells. Early results in eight patients so far are promising.”

Miami Cancer Institute is the only Florida site for the two AML trials, which are both enrolling patients.