Purpose

To determine the safety, tolerability, pharmacokinetics, maximum tolerated dose, or pharmacological active dose of BAY2402234 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML)

Condition

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])
  • 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 4 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

ArmDescriptionAssigned Intervention
Experimental
BAY2402234/ 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
BAY2402234/ 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
BAY2402234/ 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.

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467-2490

More Details

NCT ID
NCT03404726
Status
Recruiting
Sponsor
Bayer

Study Contact

Bayer Clinical Trials Contact
(+) 1-888-8422937
clinical-trials-contact@bayer.com

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.