Evaluating the Efficacy and Safety of Bemcentinib in Patients With Myelodysplastic Syndromes

NCT03824080 | Completed Phase 2

• 1 other identifier: BERGAMO_GWT12470_2017
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 8

Brief Summary

This is an open-label, single-arm multicenter, phase II study. The primary objective is to assess the efficacy of bemcentinib (BGB324) a highly selective inhibitor of the AXL receptor tyrosine kinase for the treatment of AML and MDS patients failing or being refractory to first line hypomethylating agent (HMA) treatment. Furthermore, safety, disease progression, treatment failure will be assessed. A total of 43 patients will be included in the trial.

Conditions

Acute Myeloid Leukemia; High-risk Myelodysplastic Syndrome; Low-risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Assessment of efficacy of Bemcentinib for the treatment of AML and MDS patients failing or being refractory to hypomethylating agent treatment

  Overall hematological response rate

  17 weeks

Secondary Outcomes (3)

• Disease progression

  up to 9 month

• Treatment failure

  up to 9 month

• Toxicity measured by NCI CTCAE 5.0

  up to 9 month

Other Outcomes (2)

• Immunophenotyping

  up to 9 month

• Biomarker analysis of Axl/Gas6

  up to 9 month

Study Arms (1)

Bemcentinib

EXPERIMENTAL

Bemcentinib will be self-administered orally (fasted) at a dose mentioned above for a total of at least 4 cycles without a treatment-free period in between. Responding patients (as per criteria of European LeukaemiaNet and International MDS working Group (2006)) are eligible for up to 5 additional cycles according to the maintenance daily dosing of 2 x 1 capsules of 100 mg for each 28 days cycle (up to 9 cycles in total).

Drug: Bemcentinib

Interventions

Bemcentinib DRUG

Bemcentinib will be self-administered orally (fasted) at a dose mentioned above for a total of at least 4 cycles daily. Responding patients (defined as at least stable disease) are eligible for up to 5 additional cycles according to the maintenance daily dosing of 2 x 1 capsules of 100 mg for each 28 days cycle (up to 9 cycles in total).

Bemcentinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male and female ≥ 18 years at the first screening
• Must be able to adhere to the study visit schedule and other protocol requirements
• Initial diagnosis of AML or MDS according to WHO 2016 classification
• At least one cytopenia (ANC \< 1800/μL or platelet count \< 100,000/μL or hemoglobin \< 10 g/dL)
• Failure to achieve complete or partial response or hematological improvement after at least six (azacitidine) or four (decitabine) 4-week treatment cycles administered during the past two years OR Relapse after initial complete or partial response or hematological improvement observed after at least six (azacitidine) or four (decitabine) 4-week treatment cycles administered during the past two years OR Intolerance to treatment with HMAs during the past two years
• Not eligible for allogeneic stem cell transplantation
• ≥ 5% bone marrow blasts at central morphology
• Off all other treatments for AML/MDS for at least four weeks; G-CSF and erythropoietin are - allowed before and during the study as clinically indicated
• ECOG performance status of 0-2
• Availability of blood counts and transfusion events for previous 2 months

You may not qualify if:

• Prior intensive chemotherapy for MDS or AML
• Radiotherapy or chemotherapy within the 14 days prior to the first dose of Bemcentinib being administered (other than hydroxyurea)
• History of the following cardiac conditions:
• Congestive cardiac failure of \> Class II severity according to the NYHA (defined as symptomatic at less than ordinary levels of activity)
• Ischemic cardiac event including myocardial infarction within 3 months prior to first dose
• Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic BP \>140 mmHg or diastolic BP \>90 mmHg), or need to change medication within 6 weeks of provision of consent due to lack of disease control
• History or presence of sustained bradycardia (≤ 60 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. (Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible )
• Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least Grade 3 (QTc \> 450 ms at baseline)
• Abnormal left ventricular ejection fraction on echocardiography or Multi Gated Acquisition Scan (MUGA) (less than the lower limit of normal for a patient of that age at the treating institution or \< 45 %, whichever is lower)
• 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. Please see Appendix XI for list of relevant medications
• Screening 12-lead ECG with a measurable QTc interval according to Fridericia's correction \> 450 ms
• Ongoing infection requiring systemic treatment. Patients who are on prophylactic antimicrobials or who have been afebrile for 48 hours following the initiation of antimicrobials are eligible
• Inadequate liver function as demonstrated by serum bilirubin ≥ 1.5 times the upper limits of normal range (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 times the ULN (or ≥ 5 times the ULN for AST or ALT in the presence of liver involvement by leukemia)
• Inability to tolerate oral medication
• Existing gastrointestinal disease affecting drug absorption such as celiac disease or Crohn's disease

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Groupe Francophone des Myelodysplasies: collaborator
• Amsterdam UMC, location VUmc: collaborator
• BerGenBio ASA: collaborator

Study Sites (8)

CHU Hôtel Dieu Service d'Hématologie Clinique

Nantes, Nantes Cedex 1, 44093, France

Location

Service d'Hématologie Séniors

Paris, Paris 7, 75010, France

Location

Hôpital Archet 1 Service d'Hématologie Clinique

Nice, 06200, France

Location

Universitätsklinikum Dresden

Dresden, 01307, Germany

Location

Marien Hospital GmbH

Düsseldorf, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Technische Universität München, Klinikum rechts der Isar

Munich, Germany

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

bemcentinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Uwe Platzbecker, Prof.

  Universitätsklinikum Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 31, 2019
• Study Start: December 20, 2018
• Primary Completion: July 13, 2020
• Study Completion: June 8, 2021
• Last Updated: December 21, 2021

Record last verified: 2021-12

Locations

DE (4); FR (3); NL (1)