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

ConditionsRecurrent Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Documented informed consent of the participant and/or legally authorized representative

Age: ≥ 18 years

Eastern Cooperative Oncology Group (ECOG) ≤ 2

Life expectancy > 3 months

Disqualifiers

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.

Concomitant use of proton pump inhibitor within 4-5 half-lives prior to the first dose of study drug

Trial design

Design model

Sequential

Treatments tested in this trial

  • Azacitidine

    Drug

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • PCNA Inhibitor AOH1996

    Drug

    Given PO

  • Venetoclax

    Drug

    Given PO

Treatment groups

12 Participants
are divided into 1 treatment group
Group A: Cohort I (AOH1996)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

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).

Time frame
During cycle 1 (Cycle length = 28 days)
2

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.

Time frame
Up to 2 years

Secondary outcomes

1

Response

Will evaluate in all eligible patients with a baseline assessment who start therapy (i.e., receiving at least one dose of a AOH1996). These patients will be considered in the primary analysis of response rate as the denominator, with number of responders in the numerator. Patients will have their response classified according European LeukemiaNet criteria of Dohner and others (2022). Response rates will also be explored based on number/type of prior therapy(ies).

Time frame
Up to 1 year
2

Minimal residual disease (MRD) status

Will be determined by conventional care flow cytometry assay performed locally using a 0.01% blast threshold for positivity. Will report MRD over the study period using both descriptive statistics and graphical methods.

Time frame
Up to 1 year
3

Complete remission (CR)

Will evaluate time to CR. Rates and 95% Clopper-Pearson binomial confidence interval will be calculated for the complete remission rate (CR/CRi/CRh). Response rates will also be explored based on number/type of prior therapy(ies).

Time frame
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
4

First response

Will evaluate time to first response.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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