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Testing the Addition of an Anti-cancer Drug, Navtemadlin, to the Usual Treatments (Cytarabine and Idarubicin) in Patients With Acute Myeloid Leukemia | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1

Testing the Addition of an Anti-cancer Drug, Navtemadlin, to the Usual Treatments (Cytarabine and Idarubicin) in Patients With Acute Myeloid Leukemia

A Phase 1b Study With Expansion Cohort of Escalating Doses of KRT-232 (AMG 232) Administered in Combination With Standard Induction Chemotherapy (Cytarabine and Idarubicin) in Newly Diagnosed Acute Myelogenous Leukemia (AML)

NCT04190550•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase Ib trial studies the side effects and best dose of navtemadlin when given together with the standard chemotherapy drugs cytarabine and idarubicin in patients with acute myeloid leukemia. Navtemadlin may stop the growth of cancer cells by blocking a protein called MDM2 that is needed for cell growth. Chemotherapy drugs, such as cytarabine and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving navtemadlin with cytarabine and idarubicin may stabilize cancer for longer when compared to giving usual treatments alone.

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate the toxicities of navtemadlin (KRT-232 \[AMG 232\]), cytarabine and idarubicin hydrochloride (idarubicin), and to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of KRT-232 (AMG 232), cytarabine and idarubicin. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the pharmacokinetic (PK) profiles of KRT-232 (AMG 232), cytarabine and idarubicin when used in combination. III. To evaluate p53 signaling induced by KRT-232 (AMG 232), cytarabine and idarubicin. IV. To correlate KRT-232 (AMG 232), cytarabine and idarubicin exposure with pharmacodynamics endpoints (efficacy, toxicity, changes in p53 signaling). EXPLORATORY OBJECTIVES: I. To evaluate the response rate (RR) and progression free survival (PFS) of KRT-232 (AMG 232), cytarabine and idarubicin in acute myeloid leukemia (AML). II. To evaluate potential predictive biomarkers, including MTF2 and H3K27me3, of response to KRT-232 (AMG 232), cytarabine and idarubicin in AML. III. To evaluate the pharmacodynamic (PD) effects of KRT-232 and induction chemotherapy in AML blasts. OUTLINE: This is a dose-escalation study of navtemadlin. Patients receive navtemadlin orally (PO) once daily (QD) on days 1-7, cytarabine intravenously (IV) twice daily (BID) over 3 hours on days 1-7, and idarubicin IV over 10-15 minutes on days 1-3. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with residual disease may receive cytarabine IV BID over 3 hours for 5 days and idarubicin IV over 10-15 minutes for 2 days starting between days 14-21 of cycle 1 or the second cycle of navtemadlin, cytarabine, and idarubicin. Patients who achieve a complete response (CR) or a CR with incomplete hematologic recovery (CRi) in either cycle 1 or 2 may receive cytarabine IV BID over 3 hours on days 1, 3, and 5 for 3-4 additional 28 to 35-day cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years, then every 6 months thereafter.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Newly diagnosed and previously untreated AML (except acute promyelocytic leukemia \[APL\]) (\>= 20% blasts in bone marrow or extramedullary leukemia) according to the World Health Organization (WHO), 2016 criteria. Note that patients who have received treatment with hypomethylating agents alone or in combination with venetoclax, ivosidenib or enasidenib for myelodysplastic syndrome (MDS) and have now transformed to AML are eligible.
•Eligible patients must show evidence of wild-type (WT) p53 as assessed by deoxyribonucleic acid (DNA) sequencing before initiation of KRT-232 (AMG 232).
•Patients must be considered candidates for intensive chemotherapy treatment with standard doses of cytarabine and idarubicin ("7+3 regimen").
•Left ventricular ejection fraction (LVEF) \>= 50% as assessed by echocardiogram or radionuclide angiography.
•All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy, except alopecia, must have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade =\< 2 prior to starting therapy.
•Patient must be willing to submit the blood sampling and bone marrow sampling for the PK and PD analyses and exploratory biomarkers.
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%).
•Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN), OR international normalized ratio (INR) \< 1.5.
•Total bilirubin =\< 2 mg/dl, unless from hemolysis, Gilbert's syndrome or liver infiltration with leukemia.
•Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN (=\< 5 x ULN if liver infiltration with leukemia).
+17 more criteria

Exclusion Criteria

•Patients with evidence of p53 mutation or deletion (e.g. chromosome 17p deletion).
•Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 2) with the exception of alopecia.
•Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug with the exception of: Hydroxyurea (HU) in patients who need to continue this agent to maintain white blood cell (WBC) count =\< 50,000/mm\^3.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to KRT-232 (AMG 232) or other agents used in study.

Locations (6)

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Northwestern University

Chicago, Illinois, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Key Dates

Start Date

February 4, 2021

Primary Completion Date

June 30, 2026

Completion Date

June 30, 2026

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Acute Myeloid LeukemiaAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Interventions

Cytarabine

DRUG

Idarubicin Hydrochloride

DRUG

Navtemadlin

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 20, 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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Testing the Addition of an Anti-cancer Drug, Navtemadlin, to the Usual Treatments (Cytarabine and Idarubicin) in Patients With Acute Myeloid Leukemia

Inclusion Criteria

Exclusion Criteria

Phase I Study of HC-7366 for Acute Myeloid Leukemia

VAC Regimen for AML Patients Who Failed to Response to VA Regimen

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

A Study of CBX-250 in Participants With Relapsed or Refractory Myeloid Leukemias

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

Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2