stop_circleTerminated/Withdrawn

Leukemia

Bayer Identifier:

19420

ClinicalTrials.gov Identifier:

NCT03404726

EudraCT Number:

2017-002896-24

EU CT Number:

Not Available
A study to investigate BAY2402234, a dihydroorotate dehydrogenase (DHODH) inhibitor, in myeloid malignancies

Trial 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).

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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)
  • - 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%

Trial summary

Enrollment Goal
40
Trial Dates
March 2018 - January 2021
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY2402234
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Institut Gustave RoussyVILLEJUIF CEDEX, 94805, France
Completed
Montefiore Medical CenterBronx, 10467-2490, United States
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Completed
Thomas Jefferson UniversityPhiladelphia, 19107, United States
Completed
Vanderbilt University Medical CenterNashville, 37232, United States

Primary Outcome

  • Maximum tolerated dose (MTD)
    The MTD was defined as the maximum dose administered during Cycle 1 at which the estimated dose-limiting toxicity (DLT) probability is closest to 30%.
    date_rangeTime Frame:
    Up to 42 days after the first dose
  • Number of subjects with DLTs
    A dose-limiting toxicity (DLT) was defined as any of the events that are clearly unrelated to underlying disease and occurring at any particular dose level during the first 28 days (i.e. Cycle 1) of treatment for non-hematological DLTs, or 42 days after the start of treatment, in the absence of active disease (i.e. < 5% blasts in bone marrow and absence of leukemic blasts in peripheral blood) for hematological DLTs. The National Cancer Institute Common Terminology Criteria for Adverse Events Version (CTCAE) v4.03 will be used to assess toxicities.
    date_rangeTime Frame:
    Up to 42 days after the first dose
  • AUC(0-24) (area under the concentration versus time curve from time zero to 24 hours) after single dose on Cycle 1 Day 1 (C1D1)
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D1
  • Cmax (maximum observed drug concentration in plasma after single dose administration) on C1D1
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
  • AUC(0-24)md (AUC(0-24) after multiple dose) on Cycle 1 Day 15 (C1D15)
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D15
  • Cmax,md (Cmax after multiple dose) on C1D15
    date_rangeTime Frame:
    Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
  • Number of subjects with Treatment Emergent Adverse Events (TEAEs)
    An AE was any untoward medical occurrence (i.e. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study.
    date_rangeTime Frame:
    From first application of study intervention up to 30 days after end of treatment

Secondary Outcome

  • Number of acute myeloid leukemia (AML) patients with complete remission (CR) and complete response with partial recovery of peripheral blood counts (CRh)
    date_rangeTime Frame:
    Up to 6 months on average
  • Number of myelodysplastic syndrome (MDS) patients with hematologic improvement (erythroid response, platelet response, and neutrophil response)
    date_rangeTime Frame:
    Every month until disease progression or patient was withdrawn from study, up to 6 months on average

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
3

Additional Information

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