Sensitization of Non-M3 Acute Myeloid Leukemia Blasts to All-Trans Retinoic Acid by the LSD1 Inhibitor Tranylcypromine: TRANSATRA Phase I Study.

ABSTRACT: The treatment of elderly, nonfit acute myeloid leukemia (AML)/MDS patients with relapsed/refractory (R/R) disease remains challenging. As histone demethylase LSD1 (KDM1A) is a rational therapeutic target in AML, we conducted a phase I trial ("rolling-six design") with the LSD1 inhibitor tranylcypromine (TCP, dose levels [DL] 20, 40, 60, 80 mg p.o. d1-28) combined with fixed-dose ATRA (45 mg/m² p.o. d10-28) and low-dose cytarabine (LDAC, 40 mg s.c. d1-10). The primary endpoint was dose-limiting toxicity (DLT) in the first 28 days of treatment. The aim was the determination of the maximum tolerated TCP dose (MTD). Twenty-three patients with AML and 2 with MDS were accrued. TCP was administered for a median of 39.5 days (range: 11-228). No DLTs were observed at any DL; MTD could no

SUBMITTER: Kruszewski M 

PROVIDER: S-EPMC12319880 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature