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A Phase 1 Study of AOH1996 in Patients With Relapsed/Refractory Acute Myeloid Leukemia | Clinical Trials | Clareo Health

RECRUITINGPHASE1

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

NCT06763341•City of Hope Medical Center

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Documented informed consent of the participant and/or legally authorized representative
•Age: ≥ 18 years
•Eastern Cooperative Oncology Group (ECOG) ≤ 2
•Life expectancy \> 3 months
•Patients with histologically confirmed AML, according to International Consensus Classification (ICC) or World Health Organization (WHO) criteria, with refractory/relapsed (R/R) disease who have failed treatment with, or are ineligible for, available therapies known to be effective for treatment of their AML
•* Patients with extramedullary disease may be included if they also have marrow involvement
•* Patients with acute promyelocytic leukemia (APL) will not be eligible
•Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
•Ability to swallow pills
•White blood cell (WBC) ≤ 25 x 10\^9/L prior to initiation of study therapy. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required (within 14 days prior to day 1 of protocol therapy)
+12 more criteria

Exclusion Criteria

•Hematopoietic stem cell transplant within 100 days prior to day 1 of protocol therapy. Patients who have stopped calcineurin inhibitors (CNI) must be off CNIs for at least 2 weeks prior to day 1 of protocol therapy
•Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy with the following exception of hydroxyurea which is allowed prior to treatment and through cycle 1 for control of rapidly progressing leukemia
•Strong inducers or strong inhibitors of CYP enzymes (e.g., 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4), other than azole antifungals with CYP3A4 inhibition potential, or drug transporters (e.g., organic anions \[OATP1B1/1B3\], BCRP, P-gp, organic cations \[OCT1, OCT2, OCT3\], MATE1 or MATE2K), or sensitive substrates of these CYPs or drug transporters, within 4-5 half-lives or 14 days prior to the first dose of study drug, whichever is longer.
•Foods/supplements that are strong inhibitors or strong or moderate inducers of CYP3A (such as St. John's wort) within 3 days prior to initiation of and during study treatment
•Systemic steroid therapy \> 10 mg/day (≤ 10mg/day prednisone equivalent ok) or any other form of immunosuppressive medication within 14 days. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted
•Must not have received or planning to receive live vaccine while being on study or 4 weeks before and after completion of treatment
•Patients with blast phase chronic myeloid leukemia (CML)
•Patients with translocation (t)(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
•Active central nervous system (CNS) disease
•Active graft versus (vs) host disease (GVHD)
+12 more criteria

Locations (1)

City of Hope Medical Center

Duarte, California, United States

Key Dates

Start Date

July 30, 2025

Primary Completion Date

January 16, 2027

Completion Date

January 16, 2027

Last Updated

March 13, 2026

Enrollment

ESTIMATED participants

Conditions

Recurrent Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia

Interventions

Azacitidine

DRUG

Biospecimen Collection

PROCEDURE

Bone Marrow Aspiration

PROCEDURE

PCNA Inhibitor AOH1996

DRUG

Venetoclax

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 13, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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

Inclusion Criteria

Exclusion Criteria

Testing the Anti-cancer Drug, Cirtuvivint, and Its Combination With ASTX727 to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes

SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation

Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

BCL2i CLAG-M in R/R Acute Myeloid Leukemia

CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia