Relapsed or Refractory Acute Myeloid Leukemia

A Phase I/II Trial of 8-Chloro-adenosine in Relapsed or Refractory Acute Myeloid Leukemia

This phase I/II trial will assess the safety and efficacy of 8-Chloro-Adenosine (8-Cl-Ado), a new therapeutic small molecule that is preferentially toxic to cancer as opposed to normal cells. It has shown potent anticancer activity against leukemia cells and has been very well tolerated in an earlier human clinical trial evaluating safety for different blood cancer.

Lay Abstract

We developed a novel drug, called 8-chloro-adenosine (8-chloro-ado), that can prevent the RNA in leukemia cells from replicating, causing the cells to die. We have conducted a phase 1 clinical trial of this drug in patients with recurrent/refractory acute myelogenous leukemia (AML), where we administered it directly into the blood vessels for one hour daily for five days. The protocol was based on our compelling studies in cell cultures and animals showing that cell lines and patient leukemia cells are sensitive to this drug at low concentrations. Twenty heavily previously treated, older (average age 68), poor risk patients (eight with previous myelodysplastic syndrome (MDS) and eight with previous bone marrow transplant) were admitted to the trial. Of note all patients’ leukemia cells from their bone marrow taken before treatment with 8-chloro-ado were sensitive to the drug. Potential heart toxicity was witnessed with the one-hour infusion and with FDA approval, the infusion length was changed to four hours daily for five days to help reduce side effects. As a result, five of the six patients treated at the current dose showed a dramatic but short-lived reduction in leukemia cells in their blood. We have now demonstrated increased killing of leukemia cells by combining 8-chloro-ado with the approved AML drug venetoclax in cell lines and animal studies and plan to advance this combination in our next clinical trial. This will allow us to treat patients with AML earlier in their disease course, ultimately improving health outcomes for these patients.