Phase I Trial with single dose of Actimab-A
In collaboration with Memorial Sloan Kettering Cancer Center (MSKCC) we are conducting a first-in-man Phase I dose escalation trial to determine the safety, pharmacology, and biological activity of Actimab-A in Acute Myeloid Leukemia (AML). Eighteen patients (median age, 64 yrs; range, 45–80 yrs) with relapsed/refractory AML were treated to date. Patients received a single infusion of Actimab-A at doses of 0.5, 1, 2, 3, or 4 µCi/kg (µCi –microCurie; total dose, 23–390 µCi). No acute toxicities were seen. Dose limiting toxicity (DLT) was suppression of the entire bone marrow lasting over 35 days and consequent death due to sepsis. It occurred in one patient treated with 3 µCi/kg and in both patients receiving 4 µCi/kg. Toxicities outside of the target organ (bone marrow) were limited to transient grade 2/3 liver function abnormalities. With follow-up from 1–24 months (median, 2 months), no evidence of damage to kidneys due to radiation was seen. Peripheral blood blasts (leukemia cells) were eliminated in 10 of 16 evaluable patients who received a full treatment dose. Bone marrow blast reductions of over 33% were seen in 10 of 15 evaluable patients at 4 weeks, including 3 patients with 5 percent or fewer blasts. Actimab-A is tolerable at doses less than 4 µCi/kg and has antileukemic activity.
Acute Myeloid Leukemia is characterized by very high numbers of immature cancerous white blood cells of certain kind that are similar to normal young blood cells and all immature white blood cells are called blasts. It is not normal for a person to have any blasts circulating in peripheral blood (peripheral blasts) and to have more than 5 percent of blasts in the bone marrow.
Phase I/II AML Trial with two consecutive fractionated doses of Actimab-A
After receiving clearance from the FDA the Company started Phase I/II multi-center AML trial with fractionated doses of Actimab-A. ATNM has concluded contracts with and provided training to 6 participating trial centers (Baylor University Medical Center, MSKCC, Johns Hopkins Medicine, University of Pennsylvania Health System, and Fred Hutchinson Cancer Center). The Phase I (dose escalating) portion of the trial is ongoing. For the proposed Phase I/II study, patients are eligible if they have previously untreated newly diagnosed acute myeloid leukemia according to World Health Organization criteria, are age 60 years or older, and are unfit for or decline intensive chemotherapy, or are 70 years or older with newly diagnosed AML. This target population has had better outcomes than relapsed and refractory patients who have been most of the patients in ATNM’s previous trials.
Maximum enrollment in the Phase I portion of the trial is 21 patients in dose escalating cohorts of 3 patients each with the goal of determining the maximum tolerated dose (MTD) for Actimab-A. There is a six week interval between dose levels. Once MTD has been determined, it will be used as the dose level for the Phase II portion of the trial which will enroll up to 53 patients. There are 4 planned dose levels in the Phase I portion of the trial.