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

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ClinicalTrials.gov Identifier: NCT02488408
Recruitment Status : Recruiting
First Posted : July 2, 2015
Last Update Posted : May 17, 2017
Sponsor:
Information provided by (Responsible Party):
BerGenBio ASA

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: BGB324 Drug: Cytarabine Drug: Decitabine Phase 1 Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Multicenter Open-label Study of BGB324 as a Single Agent and in Combination With Cytarabine or Decitabine in Patients With Acute Myeloid Leukemia or as a Single Agent in Patients With Myelodysplastic Syndrome
Actual Study Start Date : September 2014
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018


Arm Intervention/treatment
Experimental: Part A
To identify the maximum tolerated dose (MTD) of BGB324 in patients with relapsed or refractory AML following treatment with cytotoxic chemotherapy or a targeted or biologic agent, or in patients with high risk MDS (Norway only).
Drug: BGB324
Experimental: Part B

To identify the safety and tolerability of BGB324:

  • as a single agent in patients with AML who are unsuitable for intensive chemotherapy
  • in a combination with cytarabine in patients with AML who are unsuitable for intensive chemotherapy
  • in a combination with decitabine in patients with AML who are unsuitable for intensive chemotherapy (US only)
  • as a single agent in patients with previously treated MDS (US Only) or in patients with high/intermediate (int-2) risk MDS (Norway Only)
Drug: BGB324
Drug: Cytarabine
Low dose cytarabine will be administered with BGB324 at a dose selected dose from Part A of the study
Other Name: Ara-C

Drug: Decitabine
Decitabine will be administered with BGB324 at a dose selected dose from Part A of the study




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of BGB324 [ Time Frame: 15 Months ]
    Dose confirmation for Phase II



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed written informed consent
  2. 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)
  3. Age 18 years or older
  4. 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.
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

  1. Patients who have a matched donor and are candidates for allogeneic bone marrow transplantation
  2. Pregnant or lactating
  3. 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).
  4. Congestive cardiac failure of >Grade 2 severity according to the NYHA defined as symptomatic at less than ordinary levels of activity
  5. 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
  6. Ischemic cardiac event including myocardial infarction within 3 months prior to first dose
  7. 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.
  8. 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.
  9. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
  10. Radiotherapy or chemotherapy within the 14 days prior to the first dose of BGB324 being administered (other than hydroxyurea)
  11. Active, uncontrolled central nervous system (CNS) disease including CNS leukemia
  12. Major surgery within 28 days prior to the start of BGB324 - excluding skin biopsies and procedures for insertion of central venous access devices
  13. Prior exposure to Astellas ASP2215.
  14. Unresolved CTCAE >Grade 2 toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia.

Full eligibility criteria available in the Protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02488408


Contacts
Contact: Murray Yale, MD, PhD +44 7557 818330 murray.yule@bergenbio.com
Contact: Sonja Loges, MD, PhD +49 407-410-51969 s.loges@uke.de

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Karen Parrott    319-353-6347    karen-parrott@uiowa.edu   
Principal Investigator: Carlos E Vigil, MD         
United States, Ohio
James Cancer Hospital & Solove Research Institute Recruiting
Columbus, Ohio, United States, 43210
Contact: Molly Vittorio    614-293-7940    molly.vittorio@osumc.edu   
Principal Investigator: William Blum, Professor         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Cora Cheung    713-792-3461    cmcheung@mdanderson.org   
Principal Investigator: Jorge Cortes, Professor         
Germany
Universitätsklinikum Frankfurt, Medizinische Klinik II Recruiting
Frankfurt, Germany, 60596
Contact: Laura Hefermehl    +49 69 6301 86708    Laura.Hefermehl@kgu.de   
Principal Investigator: Jörg Chromik, Dr         
University Medical Center Hamburg-Eppendorf Martinistrasse Recruiting
Hamburg, Germany, 20246
Contact: Sonja T Loges, MD, PhD    +49 407-410-51969    s.loges@uke.de   
Principal Investigator: Sonja Loges, MD, PhD         
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Gabriele Samson    +49 (511) 532 9321    samson.gabriele@mh-hannover.de   
Principal Investigator: Michael Heuser, Dr         
Universitätsklinikum Ulm, Oberer Eselsberg, Zentrum für Innere Medizin III Recruiting
Ulm, Germany, 89081
Contact: Manuela Wetzel    +49 (0) 731 500 45709    manuela.wetzel@uniklinik-ulm.de   
Principal Investigator: Peter Paschka, Dr         
Norway
Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Contact: Marianne Emblem Lehmann    +47 59972890/ 95975516    marianne.emblem.lehmann@helse-bergen.no   
Principal Investigator: Bjørn Tore Gjertsen, Professor         
Sponsors and Collaborators
BerGenBio ASA
Investigators
Principal Investigator: Sonja Loges, MD, PhD University Medical Center Hamburg-Eppendorf Martinistrasse

Additional Information:
Publications:
Responsible Party: BerGenBio ASA
ClinicalTrials.gov Identifier: NCT02488408     History of Changes
Other Study ID Numbers: BGBC003
First Posted: July 2, 2015    Key Record Dates
Last Update Posted: May 17, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Decitabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors