NTX-301 in MDS/AML

NCT04167917 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-300004830Southern Research
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

NTX-301 is a DNMT1 inhibitor. The drug is an oral drug with preclinical data that has shown preclinical anti-leukemic efficacy. This is the first clinical trial using NTX-301 in patients with myeloid malignancies.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety/tolerability: Incidence of treatment related adverse events (AEs) and dose-limiting toxicities (DLTs)

  3 years

Secondary Outcomes (9)

• Efficacy: Clinical Benefit Rate (CBR)

  3 years

• Efficacy: Overall response rate (ORR)

  3 years

• Efficacy: Progression free survival (PFS)

  3 years

• Efficacy: Overall survival (OS)

  3 years

• Pharmacodynamics (PD): Global methylation (assay) in blood and/or marrow leukemia samples

  3 years

Study Arms (1)

NTX-301

EXPERIMENTAL

Drug: NTX-301

Interventions

NTX-301 DRUG

oral hypomethylating agent

NTX-301

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
• Men or women ≥18 years with one of the following conditions that is relapsed or refractory to at least one line of therapy:
• Acute myeloid leukemia as long as with myeloblast percentage in the marrow is ≤ 30% or the peripheral white blood cell count is less than 20,000 cells/μL in the absence of leukoreducing therapy (e.g., hydroxyurea, leukapheresis)
• MDS classified as intermediate, high, or very high risk by International Prognostic Scoring System-Revised \[IPSS-R\] criteria
• CMML classified as intermediate-2 or high risk per CMML-specific prognostic scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria
• ECOG performance status of 0, 1, or 2
• Adequate organ function at screening defined as follows \[reasonably minor changes pre-first dose are acceptable if deemed so by the investigator\]:
• a) Hepatic:
• Total bilirubin ≤2 × upper limit of normal (ULN); isolated bilirubin \> 2 is acceptable if participant has a diagnosis of Gilbert's syndrome
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤3 × ULN.
• b) Renal:
• estimated glomerular filtration rate (by CKD-EPI method) ≥ 40 mL/min/1.73 m2 c) Cardiac:
• Left ventricular ejection fraction greater than 45% or the institutional lower limit of normal by either ECHO or MUGA at entry.
• Patients must have recovered to grade 1 or less from prior toxicity or adverse events (exception of myelosuppression - neutropenia, anemia, thrombocytopenia - and alopecia). Note: Participants with treatment-related toxicities that are unlikely to resolve per the investigator may be enrolled on a case-by-case basis after discussion with the medical monitor
• Patients must have completed any chemotherapy, radiation therapy, or biologic therapy specific to their myeloid neoplasm ≥ 2 weeks or 5 half-lives (whichever is longer)

You may not qualify if:

• Diagnosis or presence of any of the following:
• acute promyelocytic leukemia
• core-binding factor AML in first relapse
• extramedullary leukemia
• symptomatic or untreated Central Nervous System (CNS) disease \[note that lumbar puncture (LP) is not required for study enrollment unless there is clinical suspicion for CNS disease; patients with history of CNS disease are permitted to enroll if they have previously received appropriate therapy and CNS remission has been; participants on maintenance intrathecal chemotherapy may be enrolled and continue to receive therapy\]
• Patients who are receiving any other investigational agents.
• Pregnant women and women who are breastfeeding are excluded from this study.
• Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to:
• severe or uncontrolled infection
• known HIV infection requiring protease inhibitor therapy
• known Hepatitis B; defined as presence of hepatitis B surface antigen (HBsAg)
• known Hepatitis C; if Hepatitis C antibody is positive, then this is defined as positive Hepatitis C RNA polymerase chain reaction (PCR) (or comparable test)
• uncontrolled diabetes and/or hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the investigator
• Malabsorption syndrome or other conditions that would interfere with intestinal absorption.
• History of a second malignancy, excluding non-melanoma skin cell cancer, within the last three years. Participants with second malignancies that were indolent, in situ or definitively treated may be enrolled even if less than three years have elapsed since treatment. Consult the monitor if there are any queries.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Prof of Medicine

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 19, 2019
• Study Start: January 6, 2021
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (2)