NCT03983824

Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 Study of M3814 in Combination With MEC in Patients With Relapsed or Refractory Acute Myeloid Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the best dose and side effects of M3814 when given in combination with mitoxantrone, etoposide, and cytarabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). M3814 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as mitoxantrone and cytarabine, 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. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Giving M3814 in combination with mitoxantrone, etoposide, and cytarabine may lower the chance of the acute myeloid leukemia growing or spreading.

Detailed description

PRIMARY OBJECTIVE: I. To assess the safety and tolerability and determine the recommended phase two dose (RP2D) of peposertib (M3814) in combination with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To characterize the pharmacokinetic (PK) profile of MEC alone and of M3814 in combination with MEC. II. To evaluate the preliminary efficacy of M3814 in combination with MEC in patients with R/R AML as measured by the response rate (complete remission \[CR\] plus CR with incomplete count recovery \[CRi\]), duration of CR/CRi (DOR), event-free survival (EFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To evaluate correlative biomarkers of M3814 target engagement and response. II. To correlate cytogenetic and molecular abnormalities with response. III. To evaluate the rates of early mortality and allogeneic hematopoietic cell transplantation. IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to: IVa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; IVb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms. V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. OUTLINE: This is a dose-escalation study of peposertib followed by a dose-expansion study. Patients receive peposertib orally (PO) twice daily (BID) on days 2-21, mitoxantrone intravenously (IV) over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiogram (ECHO) or multigated acquisition scan (MUGA) during baseline, and blood collection and bone marrow biopsy throughout the study. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months thereafter up to 5 years.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Cytarabine	Given IV
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Etoposide Phosphate	Given IV
DRUG	Mitoxantrone Hydrochloride	Given IV
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
DRUG	Peposertib	Given PO

Timeline

• Start date: 2020-05-05
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2019-06-12
• Last updated: 2026-04-13

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated drug study