A Phase Ib / II Multicenter Open-label Study of BGB324 in Patients With AML or MDS

Status: Active

Description

A Phase Ib / II multicentre open label study of BGb324 as a single agent in patients with AML or MDS or in a combination with cytarabine and decitabine in AML patients. BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor which is overexpressed in up to half of AML cases.

Eligibility Criteria

Inclusion Criteria

  • Provision of signed written informed consent
  • Histological, molecular or cytological confirmation of: Part A:
  • AML (with the exception of AML M3), patients with relapsed or refractory AML following treatment with cytotoxic chemotherapy or a targeted or biologic agent
  • high risk group MDS, according to IPSS Risk Stratification (Norway Only) Part B:
  • AML (with the exception of AML M3):
  • AML unsuitable for intensive chemotherapy
  • newly diagnosed AML unsuitable for intensive chemotherapy
  • MDS:
  • high/intermediate (int-2) risk group MDS, according to IPSS Risk Stratification (Norway Only)
  • patients with previously treated MDS (with the exception of deletion 5q MDS) (US only)
  • Age 18 years or older
  • Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to taking their first dose of BGB324. Male patients and female patients of reproductive potential must practice highly methods of contraception throughout the study and for ≥ 3 months after the last dose of BGB324.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria

  • Patients who have a matched donor and are candidates for allogeneic bone marrow transplantation
  • Pregnant or lactating
  • Abnormal left ventricular ejection fraction (less than the lower limit of normal for a patient of that age at the treating institution or <45%, whichever is lower).
  • Congestive cardiac failure of >Grade 2 severity according to the NYHA defined as symptomatic at less than ordinary levels of activity
  • Unstable cardiac disease, including unstable angina or unstable hypertension, or need to change medication within 6 weeks of provision of consent due to lack of disease control
  • Ischemic cardiac event including myocardial infarction within 3 months prior to first dose
  • Current treatment with any agent known to cause Torsades de Pointes which cannot be discontinued at least five half-lives or two weeks prior to the first dose of study treatment.
  • Treatment with any of the following; histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 3 days or 5 half-lives of administration of BGB234, whichever is longer.
  • Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
  • Radiotherapy or chemotherapy within the 14 days prior to the first dose of BGB324 being administered (other than hydroxyurea)
  • Active, uncontrolled central nervous system (CNS) disease including CNS leukemia
  • Major surgery within 28 days prior to the start of BGB324 - excluding skin biopsies and procedures for insertion of central venous access devices
  • Prior exposure to Astellas ASP2215.
  • Unresolved CTCAE >Grade 2 toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia.

Locations & Contacts

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

This study is a dose-escalation of BGB324, an Axl kinase inhibitor, in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), followed by a cohort expansion study of BGB324 either as a single agent in patients with AML or MDS, or in combination with cytarabine (cytosine arabinoside, Ara-C) or decitabine in patients with AML. The study will run in Germany, Norway and the US and may enrol up to approximately 75 patients with AML or MDS. The study consists of a dose-escalation phase to determine the MTD and/or recommended dose for Phase II (RP2D) of BGB324 in patients with relapsed or refractory AML or MDS (Part A) followed by a cohort expansion phase in up to four disease-specific cohorts (Part B). BGB324 will be administered orally according to a daily schedule, with the first three doses of Cycle 1 serving as a 'loading' dose. Each 21-day (three week) period will constitute 1 cycle of treatment.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
BerGenBio ASA

Trial IDs

Primary ID BGBC003
Secondary IDs NCI-2015-01349
Clinicaltrials.gov ID NCT02488408