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Acute Myeloid LeukemiaPhase 2NCT03824080

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

A Phase 2 study testing Bemcentinib in people with Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome, run by GWT-TUD GmbH at 8 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bemcentinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
8 sitesin 3 countries
Study dates
20 Dec 2018to 8 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Known lactose intolerance, congenital lactase deficiency, galactosemia, Glucose-galactose malabsorption
  • 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 more than 40 mg prednisolone (or equivalent dose of systemic corticosteroid) which cannot be discontinued up to one week prior to starting Bemcentinib
  • Treatment with medications which are predominantly metabolized by CYP3A4 and have a narrow therapeutic index (examples of medication are in the appendix X15.10.2)
  • Previous bowel resection that would interfere with drug absorption
  • Impaired renal function as demonstrated by a creatinine clearance of < 30 mL/min determined by Cockcroft-Gault formula
  • Unresolved CTCAE > Grade 2 toxicity (other than stable toxicity) from previous anticancer therapy excluding alopecia
  • Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
  • Known active, uncontrolled central nervous system (CNS) disease including CNS leukemia
  • Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses - screening for viral infections is not required for entry to this study
  • Major surgery within 28 days prior to the start of Bemcentinib - excluding skin biopsies and procedures for insertion of central venous access devices
  • Patients who are unwilling to follow strict highly effective contraception requirements including combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion2, vasectomised partner, sexual abstinence, surgical sterilization)) before entry and throughout the study. Female patients with reproductive potential who do not have a negative urine ß-HCG pregnancy test at screening and not more than 3 days prior to initiation of treatment
  • Female patients who are lactating
  • Exclusion periods from other studies or simultaneous participation in other clinical studies (excluding non-interventioneal studies/registries)
  • Criteria which in the opinion of the investigator precluded participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety
  • Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site)
  • Subject is an employee of GWT-TUD GmbH or participating study groups

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

Germany4 sites

  • Universitätsklinikum Dresden

    Dresden, 01307

  • Marien Hospital GmbH

    Düsseldorf

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Technische Universität München, Klinikum rechts der Isar

    Munich

Other trials in Germany

France3 sites

  • CHU Hôtel Dieu Service d'Hématologie Clinique

    Nantes, Nantes Cedex 1, 44093

  • Hôpital Archet 1 Service d'Hématologie Clinique

    Nice, 06200

  • Service d'Hématologie Séniors

    Paris, Paris 7, 75010

Other trials in France

Netherlands1 site

  • VU University Medical Center

    Amsterdam, 1081 HV

Other trials in Netherlands

About this study

Official title: A Phase II Study Evaluating the Efficacy and Safety of Bemcentinib in Patients With Myelodysplastic Syndromes Failing Standard of Care Therapy

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.

Read the detailed description

Novel treatment options in patients with MDS or AML are urgently needed; treatment has not changed significantly over the past decades and survival is still dismal, especially in elderly patients not capable for an allogeneic stem cell transplantation and failing first line treatment with hypomethylating agents. Axl, a member of the Tyro3, Axl, Mer (TAM) receptor family, mediates proliferation and survival of leukemic cells and is upregulated upon cytostatic treatment. In addition, leukemic cells induce expression of the Axl ligand growth arrest-specific gene 6 (Gas6) in bone marrow stroma cells, which further amplifies their growth and therapy resistance. selective inhibition of Axl signaling by the small molecule Axl inhibitor bemcentinib blocked leukemic proliferation in vitro and in mouse models. It was shown that a blockade of the Gas6/Axl signaling axis by R428 (bemcentinib) significantly impaired MDS growth in an ex-vivo stroma-dependent co-culture setting using patient-derived primary material. These effects were especially observed in the CD34+ MDS stem cell compartment. A persistence of this stem cell compartment is expected to underlie drug resistance and/or drive disease progression in MDS. Thus, Axl represents a potential novel target in higher risk MDS and AML.

Being tested
Bemcentinib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BemcentinibDrug

    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).

Study groups in NCT03824080
Study groupRoleWhat they receive
BemcentinibExperimentalBemcentinib 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).
Receives: Drug: Bemcentinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 17 weeks

Secondary outcomes (3)

  1. Disease progression

    Disease progression measured by increase of bone marrow blasts

    Measured: up to 9 month

  2. Treatment failure

    Time to treatment failure

    Measured: up to 9 month

  3. Toxicity measured by NCI CTCAE 5.0

    toxicity measured by NCI CTCAE 5.0

    Measured: up to 9 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2019
  2. Study start20 Dec 2018
  3. Primary completion13 Jul 2020
  4. Study completion8 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03824080
Sponsor's protocol ID
BERGAMO_GWT12470_2017
Status last verified
Dec 2021
First submitted
2 Jan 2019
Last updated
21 Dec 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bemcentinib in people with Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome, run by GWT-TUD GmbH at 8 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of efficacy of Bemcentinib for the treatment of AML and MDS patients failing or being refractory to hypomethylating agent treatment (time frame: 17 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03824080.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2021.

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