Background: Ven is a BCL2 inhibitor that is approved in combination with lower intensity therapy for pts with newly diagnosed AML who are ineligible for intensive chemo. We previously reported the safety and efficacy of cladribine and araC with idarubicin in young and fit pts with AML. Here, we studied the combination of ven with the intensive CLIA regimen in newly diagnosed AML. Methods: Pts < 65 yrs with newly diagnosed FLT3-wildtype AML were enrolled. Induction was cladribine 5 mg/m² IV on D 1-5, followed by ara-C 1.5 g/m² IV on D 1-5, idarubicin 10 mg/m² IV D 1-3, and ven at an effective dose of 400mg PO on D2-8. There was no ramp up for ven and dose modifications for CYP3A4 inhibitors were made. Consolidation consisted of up to 5 more cycles of CLIA+Ven. All pts underwent baseline next generation sequencing and MRD testing by multiparameter flow cytometry at the time of response. Results: 18 pts are enrolled, with a median age of 50 yrs (range, 18-64). Baseline pt characteristics are in Table. 16 pts were evaluable for response and 2 are too early. 14 of 16 pts (88%) achieved a remission, including 10 (63%) complete remission (CR) and 4 (25%) CR with incomplete count recovery (CRi). The median time to response was 1 cycle and the median number of cycles given was 2 (1-5). 10 of the 14 responders (71%) had undetectable MRD at the time of remission. Both nonresponding pts had a complex karyotype and 1 had a TP53 mutation. With a median follow up of 4.5 months (0.2 – 11.2), none of the responding pts have relapsed. 8 of the 14 responders (57%) have received allogeneic stem cell transplant. The median survival has not been reached; the 6-month OS and RFS are 90% and 100%, respectively. Treatment was well tolerated, with 0% 4-week mortality. The median days to ANC ≥ 1 and Platelets ≥ 100 were 30 (19-49) and 26 (18-39), respectively. Tumor lysis syndrome was not seen. The most common adverse events were neutropenic fever, pneumonia, nausea, and liver transaminitis. Conclusions: The addition of ven to CLIA was safe and effective in newly diagnosed pts with AML. The combination was not associated with early mortality or prolonged myelosuppression, but did result in high rates of durable MRD negative remissions. Clinical trial information: NCT02115295.