NCT04190550

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)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV
DRUG	Idarubicin Hydrochloride	Given IV
DRUG	Navtemadlin	Given PO

Timeline

• Start date: 2021-02-04
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2019-12-09
• Last updated: 2026-04-13

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study