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Trial details
CMBG453B12301 Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Current status:
Approved
|
Date registered:
30/12/2021
Trial version(s)
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
History: 18/09/2020
Current: 18/09/2020
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Main Information
Primary registry identifying number
LBCTR2020094590
Protocol number
CMBG453B12301
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Novartis Pharmaceuticals
Primary sponsor: Country of origin
Novartis Pharmaceuticals
Public title
CMBG453B12301 Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Acronym
CMBG453B12301
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Acronym
Brief summary of the study: English
This is a Phase III multi-center, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to azacitidine in adult subjects with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) who have an indication for treatment with azacitidine in first-line setting and are not eligible for intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) according to medical judgment by the investigator. The purpose of the current study is to assess clinical effects of MBG453 in combination with azacitidine in adult subjects with IPSS-R intermediate, high, very high risk MDS and CMML-2.
Brief summary of the study: Arabic
دراسة متعددة المراكز، عشوائیّة التوزیع، مزدوجة التعمیة، مرتكزة على المقارنة بدواء وھمي، في المرحلة الثالثة حول دواء أزاسیتیدین مع أو لعلاج المرضى المصابین بمتلازمة خلل التنسّج النقوي MBG بدون 453 العالیة الخطورة أو ذات الخطورة العالیة جداً وفقاً للنظام الدولي المنقحّ أو بسرطان الدم الوحیديّ النقويّ المزمن- 2 (IPSS-R) لتسجیل النتائج
Health conditions/problem studied: Specify
•Myelodysplastic Syndromes •Leukemia, Myelomonocytic, Chronic
Interventions: Specify
•Drug: MBG453 A dose of MBG453 800 mg will be administered intravenously (IV) every 4 weeks (Q4W). •Drug: Azacitidine A dose of Azacitidine 75 mg/m2 will be administered IV or subcutaneously (SC) on Day 1-7, or Day 1-5, 8 and 9. •Drug: Placebo A dose of Placebo 800 mg will be administered intravenously every 4 weeks (Q4W).
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion Criteria: •Signed informed consent must be obtained prior to participation in the study •Age ≥ 18 years at the date of signing the informed consent form •Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R): ◦Very high (> 6 points) ◦High (> 4.5 - ≤ 6 points) ◦Intermediate (> 3 - ≤ 4.5 points) Or Morphologically confirmed diagnosis of Chronic Myelomonocytic Leukemia -2 based on WHO 2016 classification (Arber et al 2016) by local investigator assessment with WBC < 13 x 109/L •Indication for azacitidine treatment according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions •Not eligible at time of screening for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities and performance status •Not eligible at time of screening for hematopoietic stem cell transplantation (HSCT) according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions, including assessment of individual clinical factors such as age, comorbidities, performance status, and donor availability •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
•Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune checkpoint inhibitors (e.g, anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines is allowed except if the drug was administered within 4 months prior to randomization •Previous first-line treatment for intermediate, high, very high risk myelodysplastic syndromes (based on IPSS-R) or CMML with any antineoplastic agents including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitibine and azacitidine. However, previous treatment with hydroxyurea or leukopheresis to reduce WBC count is allowed prior to randomization. •Investigational treatment received within 4 weeks or 5 half-lives of this investigational treatment, whatever is longer, prior to randomization. In case of a checkpoint inhibitor: a minimal interval of 4 months prior to randomization is necessary to allow randomization. •Subjects with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3 •Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia, primary or secondary myelofibrosis based on WHO 2016 classification (Arber et al 2016) •Diagnosis of therapy related myeloid neoplasms based on WHO 2016 classification (Arber et al 2016) •History of organ or allogeneic hematopoietic stem cell transplant Other protocol-defined Inclusion/Exclusion Criteria may apply.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
MBG453
Type of IMP
Immunological
Pharmaceutical class
humanized monoclonal antibody against human TIM-3
Therapeutic indication
Patients with: Myelodysplastic Syndromes or with chronic Leukemia Myelomonocytic
Therapeutic benefit
The primary objective of this study is to compare overall survival (OS) in the MBG453 plus azacitidine arm versus placebo plus azacitidine arm where OS is the time from randomization until death due to any cause.
Biospecimen retention
Samples without DNA
Biospecimen description
Samples will be shipped to covance central laboratory and BMA will be
Target sample size
4
Actual enrollment target size
1
Date of first enrollment: Type
Actual
Date of first enrollment: Date
05/07/2021
Date of study closure: Type
Actual
Date of study closure: Date
25/11/2027
Recruitment status
Recruiting
Date of completion
29/07/2022
IPD sharing statement plan
Yes
IPD sharing statement description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
Additional data URL
https://clinicaltrials.gov/ct2/show/record/NCT04266301?term=MBG&draw=2&rank=2&view=record
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Clinical trials.gov
NCT04266301
Sources of Monetary or Material Support
Name
Novartis Pharmaceuticals
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Ali
Bazarbachi
Beirut
Lebanon
961-1-350000 ext 5800
bazarbac@aub.edu.lb
American University of Beirut Medical Center
Scientific
Hind
Khairallah
Beirut
Lebanon
9611512002 ext 271
hind.khairallah@fattal.com.lb
Khalil Fattal et Fils
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American UNiversity of Beirut medical Center
Ali Bazarbachi
Hematology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
31/08/2020
Fuad Zyiadeh
fz05@aub.edu.lb
9611350000 ext 5445
Countries of Recruitment
Name
Lebanon
Australia
Austria
Belgium
Oman
Saudi Arabia
Czech Republic
Finland
France
Japan
Singapore
Spain
Switzerland
Taiwan
Thailand
Health Conditions or Problems Studied
Condition
Code
Keyword
MDS
Myelodysplastic syndrome, unspecified (D46.9)
MDS
CMML 2
Chronic monocytic leukaemia (C93.1)
CMML2
Interventions
Intervention
Description
Keyword
Informed consent, IMP administration, questionnaire , Bone marrow aspirate, Lab tests
Informed consent, IMP administration, questionnaire , Bone marrow aspirate, Lab tests
Informed consent, IMP administration, questionnaire , Bone marrow aspirate, Lab tests
Primary Outcomes
Name
Time points
Measure
Overall Survival
5 years
5 years
Key Secondary Outcomes
Name
Time points
Measure
Time to definitive deterioration of fatigue using Functional Assessment of Cancer Therapy (FACIT)-Fatigue score
5 years
5 years
Red Blood Cell transfusion-free intervals
5 years
5 years
Percent of subjects with at least 3 point confirmed improvement from baseline in FACIT-fatigue scoresscore
5 years
5 years
Percent of subjects with at least 10 point confirmed improvement from baseline in physical functioning using European Or ganization for Research and Treatment of Cancer's Core Quality of Life Questionnaire
5 years
5 years
Percentage of subjects with either CR, or mCR, or PR, or HI in each treatment arm according to International Working Group for MDS
5 years
5 years
Progression Free Survival (PFS)
5 years
5 years
Percentage of subjects with stable disease in each treatment arm according to International Working Group for MDS (IWG-MDS) as per investigator assessment
5 years
5 years
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Annual submission 2021
26/12/2021
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