Clinical Trials /

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

NCT03404726

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Investigate BAY2402234, a Dihydroorotate Dehydrogenase (DHODH) Inhibitor, in Myeloid Malignancies
  • Official Title: An Open-label, Multicenter Phase 1 Study to Characterize the Safety, Tolerability, Preliminary Antileukemic Activity, Pharmacokinetics, and Maximum Tolerated Dose or Pharmacological Active Dose of BAY2402234 in Patients With Advanced Myeloid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 19420
  • SECONDARY ID: 2017-002896-24
  • NCT ID: NCT03404726

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
BAY2402234Dose Escalation

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).

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose 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
  • BAY2402234
Dose Expansion: AMLExperimentalAfter 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.
  • BAY2402234
Dose Expansion: MDSExperimentalAfter 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.
  • BAY2402234

Eligibility Criteria

        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%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:Up to 42 days after the first dose
Safety Issue:
Description:Phase 1 dose escalation study with increasing doses of study drug (BAY2402234). Maximum tolerated dose will be defined as the maximum dose administered during Cycle 1 at which the incidence of dose limiting toxicities is closest to 30%.

Secondary Outcome Measures

Measure:Composite endpoint: Number of AML patients with complete remission (CR) and complete response with partial recovery of peripheral blood counts (CRh)
Time Frame:Up to 6 months on average
Safety Issue:
Description:Response criteria according to modified IWG 2003. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter)
Measure:Change in erythroid response as Histological Improvement criteria for patients with MDS and CMML
Time Frame:Every month until disease progression or patient is withdrawn from study, up to 6 months on average
Safety Issue:
Description:Response criteria according to IWG 2006.
Measure:Change in platelet response as Histological Improvement criteria for patients with MDS and CMML
Time Frame:Every month until disease progression or patient is withdrawn from study, up to 6 months on average
Safety Issue:
Description:Response criteria according to IWG 2006.
Measure:Change in neutrophil response as Histological Improvement criteria for patients with MDS and CMML
Time Frame:Every month until disease progression or patient is withdrawn from study, up to 6 months on average
Safety Issue:
Description:Response criteria according to IWG 2006.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Acute myeloid leukemia
  • Myelodysplastic Syndromes
  • Chronic myelomonocytic leukemia
  • Dihydroorotate dehydrogenase (DHODH) inhibitor

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