NCT06763341

A Phase 1 Study of AOH1996 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase 1 trial tests safety, side effects, and best dose of AOH1996 for the treatment of patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or AML that has not responded to previous treatment (refractory). AOH1996 is in a class of medications called PCNA inhibitors. It inhibits cancer growth and induces deoxyribonucleic acid (DNA) damage. This may help keep cancer cells from growing and damage cancer cell DNA. Giving AOH1996 may be safe, tolerable and/or effective in treating patients with AML.

Detailed description

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of AOH1996 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). II. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AOH1996. SECONDARY OBJECTIVES: I. Evaluate the anti-leukemic activity, as assessed by complete remission (CR) rate at the end of cycles 1 and 2. II. Evaluate the anti-leukemic activity, as assessed by overall response rate (\[ORR\]: CR+CR with incomplete hematologic recovery rate \[CRi\]+CR with partial hematologic recovery \[CRh\]+morphologic leukemia-free state \[MLFS\] + partial remission \[PR\]) at the end of cycles 1 and 2. III. Evaluate the anti-leukemic activity, as assessed by complete remission (CR), overall response (ORR: CR+CRi+CRh+PR) and minimal residual disease (MRD)- rate and duration over the study period. IV. Evaluate transfusion independence (TI). V. Estimate overall survival (OS) rate, progression-free survival (PFS) and duration of response (DOR) rate at 6 months and 1 year. VI. Describe the plasma pharmacokinetics (PK) of AOH1996 alone. EXPLORATORY OBJECTIVES: I. Determine biomarkers that may be predictive of AOH1996 activity. II. Study the impact of AOH1996 on altered mitochondrial metabolism and dynamics. III. Determine pharmacodynamics (PD) parameters (alteration of OPA1) of AOH1996. IV. Estimate leukemia stem cell burden in bone marrow pre-, post-therapy. OUTLINE: This is a dose-escalation study of AOH1996. COHORT I: Patients receive AOH1996 orally (PO) twice daily (BID) on days 1 - 28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients that attain a CR/CRh/CRi with transfusion independence (TI) by the end of cycle 2 continue cycles every 28 days for up to 12 total cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 30 days and up to one year.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
DRUG	PCNA Inhibitor AOH1996	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2025-07-30
• Primary completion: 2027-01-16
• Completion: 2027-01-16
• First posted: 2025-01-08
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study