RECRUITING

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

Conditions

Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-08-16

Study Completion:2027-08-16

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06763341

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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) * 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) * Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days prior to day 1 of protocol therapy) * Corrected QT interval (QTc)F ≤ 480 ms based on Fridericia's formula * Note: To be performed within 28 days prior to day 1 of protocol therapy * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential\* to use an effective method of birth control (nonhormonal) or abstain from heterosexual activity for the course of the study through at least 2 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)	* 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 * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Uncontrolled active infection * Clinically significant uncontrolled illness * Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Females only: Pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Inclusion Criteria

Exclusion 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)
* 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)
* Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
* Corrected QT interval (QTc)F ≤ 480 ms based on Fridericia's formula
* Note: To be performed within 28 days prior to day 1 of protocol therapy
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential\* to use an effective method of birth control (nonhormonal) or abstain from heterosexual activity for the course of the study through at least 2 months after the last dose of protocol therapy
* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

* 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
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Uncontrolled active infection
* Clinically significant uncontrolled illness
* Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Amanda Blackmon

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Amanda Blackmon, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-16

Study Completion Date2027-08-16

Study Record Updates

Study Start Date2025-08-16

Study Completion Date2027-08-16

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia