Vanderbilt Clinical Trials

A Study to Investigate BAY2402234, a Dihydroorotate Dehydrogenase (DHODH) Inhibitor, in Myeloid Malignancies

Purpose

The primary objective is to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), or pharmacological active dose (PAD) of BAY2402234 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). The secondary objective is to evaluate evidence of clinical efficacy associated with BAY2402234 in patients with AML (defined as Complete remission, Complete remission with partial hematologic recovery), and MDS (defined as hematological improvement).

Condition

Leukemia

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Patients with relapsed or refractory AML. Relapsed AML is defined as relapse after achieving a response to initial therapy and refractory AML is defined as failure to achieve a response after one previous line of therapy. Response is defined as per IWG criteria (CR, CRi or CRp). Patients who are not candidates to receive or who decline standard of care therapy are also eligible. - Patients with intermediate-1 or higher risk MDS who have failed therapy with a hypomethylating agent, or have failed lenalidomide therapy if harboring a 5q-chromosomal deletion. - Patients with relapsed/refractory CMML. - Estimated glomerular filtration rate (eGFR) > 40 mL per 1.73 m^2 - Patients must have adequate coagulation (international normalized ratio [INR] ≤ 1.5; activated partial thromboplastin time [aPTT] ≤1.5 X the upper limit of normal [ULN]; patients on chronic anticoagulation therapy at investigator's discretion; patients on chronic use of direct-acting oral anticoagulants who have acceptable benefit-risk ratio at investigator's discretion) - Adequate liver function (total bilirubin ≤1.5 X ULN (or ≤3 X ULN in patients with documented Gilbert's syndrome or for patients with hyperbilirubinemia considered due to myeloid disease), alanine aminotransferase [ALT] and aspartate aminotransferase [AST] ≤3 X ULN (or ≤5 X ULN for patients with liver involvement of their myeloid disease)

Exclusion Criteria

Patients eligible for hematopoietic stem cell transplantation - Clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia - Human immunodeficiency virus (HIV) infection - Chronic or active hepatitis B or C if not controlled by antiviral therapy - History of organ allograft (allogeneic bone marrow or stem cell transplant) within 3 months prior to first dose of study drug - Serious, uncontrolled infection requiring systemic antibiotic, antifungal or antiviral therapy. Prophylactic antibiotic, antifungal and/or antiviral therapy is permitted - Left ventricular ejection fraction (LVEF) <40%

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Dose Escalation	Dose escalation with sequential cohorts enrolling patients with AML, MDS, or CMML. Patients will be treated in 28-day cycles with once daily oral administration of BAY2402234	Drug: BAY2402234 BAY2402234 is a potent and selective small molecule inhibitor of dihydroorotate dehydrogenase. A solution of BAY2402234 will be available to initiate the trial and there are plans to transition to a tablet form of BAY2402234 once it becomes available. Both liquid and tablet formulations of BAY2402234 will be continually administered once daily by mouth in 28 day cycles.
Experimental Dose Expansion: AML	After completion of dose escalation, an expansion cohort comprised of patients with AML will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose.	Drug: BAY2402234 BAY2402234 is a potent and selective small molecule inhibitor of dihydroorotate dehydrogenase. A solution of BAY2402234 will be available to initiate the trial and there are plans to transition to a tablet form of BAY2402234 once it becomes available. Both liquid and tablet formulations of BAY2402234 will be continually administered once daily by mouth in 28 day cycles.
Experimental Dose Expansion: MDS	After completion of dose escalation, an expansion cohort comprised of patients with MDS will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose.	Drug: BAY2402234 BAY2402234 is a potent and selective small molecule inhibitor of dihydroorotate dehydrogenase. A solution of BAY2402234 will be available to initiate the trial and there are plans to transition to a tablet form of BAY2402234 once it becomes available. Both liquid and tablet formulations of BAY2402234 will be continually administered once daily by mouth in 28 day cycles.

More Details

Status: Terminated
Sponsor: Bayer

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.