A Phase Ib/II Multicenter Open-label Study of Bemcentinib (BGB324) in Patients With AML or MDS
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|ClinicalTrials.gov Identifier: NCT02488408|
Recruitment Status : Active, not recruiting
First Posted : July 2, 2015
Last Update Posted : March 2, 2022
A Phase Ib/II multicentre open label study of bemcentinib (BGB324) as a single agent in participants with Acute Myeloid Leukemia (AML) or Myelodysplastic syndrome (MDS) or in a combination with cytarabine or decitabine in AML participants.
Bemcentinib 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: Bemcentinib Drug: Cytarabine Drug: Decitabine||Phase 1 Phase 2|
This study is a dose-escalation of bemcentinib (BGB324), a selective Axl kinase inhibitor, in participants with AML and MDS, followed by a cohort expansion study of bemcentinib either as a single agent in participants with AML or MDS, or in combination with cytarabine (cytosine arabinoside, Ara-C) or decitabine in participants with AML.
The study will run in Germany, Norway, Italy and the US and may enrol up to approximately 90 participants with AML or MDS.
The study consists of a dose-escalation phase to determine the MTD (maximum tolerated dose) and/or recommended dose for Phase II (RP2D) of bemcentinib in participants with relapsed or refractory AML or MDS (Part A) followed by a cohort expansion phase in up to four disease-specific cohorts (Part B).
Bemcentinib 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)|
|Actual Enrollment :||121 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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 :||April 2022|
|Estimated Study Completion Date :||April 2022|
Experimental: Part A
To identify the maximum tolerated dose (MTD) of bemcentinib (BGB324) in participants with relapsed or refractory AML following treatment with cytotoxic chemotherapy or a targeted or biologic agent, or in participants with high risk MDS (Norway only).- This Arm of the study has completed recruitment
Other Name: BGB324
Experimental: Part B
To identify the safety and tolerability of bemcentinib:
Other Name: BGB324
Other Name: Ara-C
Other Name: Dacogen
- Part A- Maximum tolerated dose (MTD) of bemcentinib (BGB324) [ Time Frame: 15 Months ]Dose escalation will occur continue until dose limiting toxicity occurs at which point a MTD will be determined and Dose confirmation for Phase II will be made. Dose Limiting Toxicity (DLT) will be assessed during the first 3 weeks of treatment (Cycle 1) with BGB324, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4, considered unrelated to leukemia progression or intercurrent illness
- Part B: Number of Participants with Treatment-emergent Adverse Events (TEAE) [ Time Frame: 10 months ]An adverse event (AE) is any unfavorable or unintended sign, symptom or disease temporally associated with the use of the investigational medicinal product (IMP) whether or not considered related to the study IMP.
- Part B: Number of Participants with Physical Examination, Vital Signs, Clinically Significant Clinical Laboratory Test and Electrocardiogram (ECG) Abnormalities [ Time Frame: 10 months ]Number of participants with physical examinations (including weight), vital signs (blood pressure [BP], heart rate [HR]), clinical laboratory test (including clinical chemistry, hematology and urinalysis), and ECG abnormalities will be reported.
- Part A: Number of Participants with Treatment-emergent Adverse Events [ Time Frame: 15 months ]An AE is any unfavorable or unintended sign, symptom or disease temporally associated with the use of the IMP whether or not considered related to the study IMP.
- Part A: Number of Participants with Physical Examination, Vital Signs, Clinical Laboratory Test and Echocardiogram Abnormalities [ Time Frame: 15 months ]Number of participants with physical examinations (including weight), vital signs (BP, HR), clinical laboratory test (including clinical chemistry, hematology and urinalysis), and echocardiogram abnormalities will be reported.
- Part A and B: Objective Response Rate (ORR) [ Time Frame: 15 months ]Percentage of participants with objective response according to the revised recommendations of the International Working Group (IWG) will be reported.
- Part A and B: Percentage of Participants with Stable Disease (SD) [ Time Frame: 15 months ]SD defined as having unchanged disease for at least 3 treatment cycles and as failure to achieve at least Partial Remission (PR), but not evidence of Progressive Disease (PD) for at least 3 treatment cycles.
- Part A and B: Percentage of Participants with Objective Response and Stable Disease as Estimate of Clinical Benefit [ Time Frame: 15 months ]
- Part A and B: Relapse Free Survival [ Time Frame: 15 months ]
- Part A and B: Event Free Survival [ Time Frame: 15 months ]
- Part A and B: Overall Survival [ Time Frame: 15 months ]
- Part A: Pharmacokinetics (PK) Parameter: Area Under The Curve Within A Dosing Interval (AUC0-tau) for Bemcentinib [ Time Frame: 15 months ]AUC0-tau defined as the area under the curve within a dosing interval, calculated by the linear up-log down trapezoidal method.
- Part A: Pharmacokinetics Parameter: Maximum Observed Plasma Concentration (Cmax) for Bemcentinib [ Time Frame: 15 months ]Cmax defined as the observed maximum plasma concentration after single dose administration.
- Part A: Pharmacokinetics Parameter: Time to Reach Maximum Plasma Concentration (Tmax) for Bemcentinib [ Time Frame: 15 months ]Tmax defined as the time to reach Cmax.
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
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52242|
|United States, Texas|
|The University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Frankfurt, Germany, 60596|
|University Medical Center Hamburg|
|Hamburg, Germany, 20246|
|Medizinische Hochschule Hannover|
|Hannover, Germany, 30625|
|Universitätsmedizin Mannheim, Universitätsklinikum Mannheim GmbH|
|Ulm, Germany, 89081|
|Azienda Ospedaliera S.|
|Cuneo, Italy, 12100|
|University of Genoa|
|Genoa, Italy, 6 16132|
|U.O. Ematologia - P.O. Vito Fazzi|
|Lecce, Italy, 73100|
|Azienda Ospedaliero-Universitaria di Parma|
|Parma, Italy, 14 43126|
|Haukelands University Hospital|
|Bergen, Norway, 5021|
|Principal Investigator:||Sonja Loges, MD, PhD||Universitätsmedizin Mannheim, Universitätsklinikum Mannheim GmbH|