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

NCT06763341 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 24727NCI-2024-10209P30CA033572
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicity (DLT)

  Will evaluate for DLTs in patients that receive at least 75% of the planned dose(s) of AOH1996 per dose level assignment. In-evaluable subjects will be replaced. Will grade toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  During cycle 1 (Cycle length = 28 days)

• Incidence of adverse events

  Will evaluate toxicity in patients that receive any AOH1996. Will grade toxicity according to the NCI CTCAE v5.0. Will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 2 years

Secondary Outcomes (8)

• Response

  Up to 1 year

• Minimal residual disease (MRD) status

  Up to 1 year

• Complete remission (CR)

  From start of treatment to attainment of CR/CR with incomplete hematologic recovery rate (CRi)/CR with partial hematologic recovery (CRh), assessed up to 1 year

• First response

  From start of treatment to attainment of first documented CR/CRi/CRh/morphologic leukemia-free state/partial response, assessed up to 1 year

• Duration of response (DOR)

  Time interval from the date of first documented response (CR+CRi+CRh) to the date of documented disease relapse or death whichever occurs first, assessed up to 2 years

Study Arms (1)

Cohort I (AOH1996)

EXPERIMENTAL

Patients receive AOH1996 PO 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.

Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: PCNA Inhibitor AOH1996; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Cohort I (AOH1996)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort I (AOH1996)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Cohort I (AOH1996)

PCNA Inhibitor AOH1996 DRUG

Given PO

Also known as: AOH1996, Proliferating Cell Nuclear Antigen Inhibitor AOH1996, AOH

Cohort I (AOH1996)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Cohort I (AOH1996)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (within 14 days prior to day 1 of protocol therapy)
• Aspartate aminotransferase (AST) =\< 3.0 x ULN (within 14 days prior to day 1 of protocol therapy)
• Alanine aminotransferase (ALT) =\< 3.0 x ULN (within 14 days prior to day 1 of protocol therapy)
• Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 14 days prior to day 1 of protocol therapy)
• International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)

You may not qualify if:

• 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)
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• Uncontrolled atrial fibrillation or hypertension
• No measurable disease in the bone marrow
• Gastrointestinal disorder that interferes with oral drug absorption such as malabsorption syndrome

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Specimen Handling; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Amanda Blackmon

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 8, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): January 16, 2027
• Study Completion (Estimated): January 16, 2027
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

US (1)