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|Ref Type||Journal Article|
|Authors||Liva SG, Coss CC, Wang J, Blum W, Klisovic R, Bhatnagar B, Walsh K, Geyer S, Zhao Q, Garzon R, Marcucci G, Phelps MA, Walker AR|
|Title||Phase I study of AR-42 and decitabine in acute myeloid leukemia.|
|Journal||Leukemia & lymphoma|
|Abstract Text||This phase I trial sought to determine a biologically safe and effective dose of AR-42, a novel histone deacetylase inhibitor, which would lead to a doubling of miR-29b prior to decitabine administration. Thirteen patients with previously untreated or relapsed/refractory AML were treated at 3 dose levels (DL): AR-42 20 mg qd on d1,3,5 in DL1, 40 mg qd on d1,3,5 in DL2 and 40 mg qd on d1,3,4,5 in DL3. Patients received decitabine 20 mg/m2 on d6-15 of each induction cycle and 20 mg/m2 on d6-10 of each maintenance cycle. One DLT of polymicrobial sepsis and multi-organ failure occurred at DL3. Two patients achieved a CRi and one patient achieved a CR for an ORR of 23.1%. The higher risk features of this patient population and the dosing schedule of AR-42 may have led to the observed clinical response and failure to meet the biologic endpoint.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|AR-42||HDAC42||HDAC Inhibitor 38||AR-42 is a histone deacetylase (HDAC) inhibitor, which may lead to increased apoptosis of tumor cells and decreased tumor growth (PMID: 23178755, PMID: 21778190, PMID: 32037935).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||acute myeloid leukemia||no benefit||AR-42 + Decitabine||Phase I||Actionable||In a Phase I trial, AR-42 and Dacogen (decitabine) combination treatment in patients with acute myeloid leukemia resulted in an overall response rate of 23.1% (3/13), including one patient with complete remission and two patients with complete remission with incomplete count recovery, but the trial did not meet its biological endpoint for safety and dosing (PMID: 32037935; NCT01798901).||32037935|