Clinical Trials List
Protocol NumberCMBG453B12201
NCT Number(ClinicalTrials.gov Identfier)NCT03946670
Completed
2019-08-01 - 2024-07-15
Phase II
Recruiting2
ICD-10C88.8
Other malignant immunoproliferative diseases
ICD-10C94.40
Acute panmyelosis with myelofibrosis not having achieved remission
ICD-10C94.41
Acute panmyelosis with myelofibrosis, in remission
ICD-10C94.42
Acute panmyelosis with myelofibrosis, in relapse
ICD-10C94.6
Myelodysplastic disease, not classified
ICD-10D46.9
Myelodysplastic syndrome, unspecified
ICD-10D46.A
Refractory cytopenia with multilineage dysplasia
ICD-10D46.B
Refractory cytopenia with multilineage dysplasia and ring sideroblasts
ICD-10D46.C
Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality
ICD-10D46.Z
Other myelodysplastic syndromes
ICD-10D47.1
Chronic myeloproliferative disease
ICD-10D47.3
Essential (hemorrhagic) thrombocythemia
ICD-10D47.9
Neoplasm of uncertain behavior of lymphoid, hematopoietic and related tissue, unspecified
ICD-10D47.Z1
Post-transplant lymphoproliferative disorder (PTLD)
ICD-10D47.Z9
Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue
ICD-9238.7
Neoplasm of uncertain behavior of other lymphatic and hematopoietic tissues
A Randomized, Double-blind, Placebo-controlled Phase II Multi-center Study of Intravenous MBG453 Added to Hypomethylating Agents in Adult Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Luh Tang 無
- Chieh-Lung Cheng Division of General Internal Medicine
- 田豐銘 Division of General Internal Medicine
- - - Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- MING YAO Division of General Internal Medicine
- Chien-Chin Lin Division of Others -
- - - Division of General Internal Medicine
- Wen-Chien Chou Division of Others -
- Huai-Hsuan Huang Division of General Internal Medicine
- 林建廷 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS)
Objectives
Primary objective(s)
To determine if MBG453 combined with standard HMA therapy improves complete remission in subjects with intermediate, high, or very high risk MDS
To determine if MBG453 combined with standard HMA therapy improves PFS in subjects with intermediate, high or very high risk MDS
Secondary objective(s)
To assess Overall Survival in each treatment arm
To assess Leukemia-free survival in each treatment
To assess responses rate in each treatment arm
To assess duration of complete remission in each treatment arm
To assess time to complete remission in each treatment arm
To assess the improvement in RBC/platelets transfusion independence in each treatment arm.
To assess the safety profile of MBG453 when given in combination with HMA
To characterize the pharmacokinetics of MBG453 when given in combination with HMA
To evaluate immunogenicity of MBG453 when given in combination of HMA
Test Drug
MBG453
Active Ingredient
MBG453
Dosage Form
Concentrate for solutoin for infusion
Concentrate for solutoin for infusion
Concentrate for solutoin for infusion
Dosage
400mg/4ml
100mg/ml
100mg/ml
Endpoints
Primary Outcome Measures :
Complete remission (CR) rate [ Time Frame: 7 months after last patient first visit (LPFV) ]
Modified response criteria According to International Working Group (IWG) for Myelodysplastic syndromes (MDS) as per investigator assessment.
Progression Free Survival (PFS) [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment
Secondary Outcome Measures :
Overall Survival [ Time Frame: Up to 4 years after LPFV ]
Time from randomization to death due to any cause
Event Free Survival [ Time Frame: Up to 4 years after LPFV ]
Time from randomization to lack of reaching CR within the first 6 months, relapse from CR or death due to any cause, whichever occurs first
Leukemia-free survival [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Time from randomization to ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification)or diagnosis of extramedullary acute leukemia or death due to any cause
Response Rate (CR/mCR/PR/HI) [ Time Frame: 7 months after Last Patient First Visit (LPFV) ]
Percentage of complete remission(CR)/marrow Complete Remission (mCR)/partial remission (PR) and Hematological improvement (HI) according to IWG-MDS as per investigator assessment
Duration of complete remission [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first
Time to complete remission [ Time Frame: 7 months after Last Patient First Visit (LPFV) ]
Time from randomization to the first documented CR
Percent of subjects who are red blood cells (RBC)/platelets transfusion independent after randomization as per IWG-MDS [ Time Frame: Up to 4 years after last randomized patient ]
Improvement in RBC/platelets transfusion independence
Red blood cells (RBC)/platelets transfusion independence duration after randomization [ Time Frame: Up to 4 years after last randomized patient ]
Duration of transfusion independence
Serum concentrations for MBG453 [ Time Frame: At Day 8 of each cycle (1 cycle = 28 days) until cycle 6 and at day 8 of cycles 9, 12, 18 and 24, and up to 150 day of the safety follow up period ]
Pharmacokinetics of MBG453 when given in combination with hypomethylating agents (HMA)
Immunogenicity of MBG453 when given in combination of hypomethylating agents [ Time Frame: Up to 4 years after Last Patient First Visit (LPFV) ]
Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment
Complete remission (CR) rate [ Time Frame: 7 months after last patient first visit (LPFV) ]
Modified response criteria According to International Working Group (IWG) for Myelodysplastic syndromes (MDS) as per investigator assessment.
Progression Free Survival (PFS) [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment
Secondary Outcome Measures :
Overall Survival [ Time Frame: Up to 4 years after LPFV ]
Time from randomization to death due to any cause
Event Free Survival [ Time Frame: Up to 4 years after LPFV ]
Time from randomization to lack of reaching CR within the first 6 months, relapse from CR or death due to any cause, whichever occurs first
Leukemia-free survival [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Time from randomization to ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification)or diagnosis of extramedullary acute leukemia or death due to any cause
Response Rate (CR/mCR/PR/HI) [ Time Frame: 7 months after Last Patient First Visit (LPFV) ]
Percentage of complete remission(CR)/marrow Complete Remission (mCR)/partial remission (PR) and Hematological improvement (HI) according to IWG-MDS as per investigator assessment
Duration of complete remission [ Time Frame: Up to 4 yrs after Last Patient First Visit (LPFV) ]
Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first
Time to complete remission [ Time Frame: 7 months after Last Patient First Visit (LPFV) ]
Time from randomization to the first documented CR
Percent of subjects who are red blood cells (RBC)/platelets transfusion independent after randomization as per IWG-MDS [ Time Frame: Up to 4 years after last randomized patient ]
Improvement in RBC/platelets transfusion independence
Red blood cells (RBC)/platelets transfusion independence duration after randomization [ Time Frame: Up to 4 years after last randomized patient ]
Duration of transfusion independence
Serum concentrations for MBG453 [ Time Frame: At Day 8 of each cycle (1 cycle = 28 days) until cycle 6 and at day 8 of cycles 9, 12, 18 and 24, and up to 150 day of the safety follow up period ]
Pharmacokinetics of MBG453 when given in combination with hypomethylating agents (HMA)
Immunogenicity of MBG453 when given in combination of hypomethylating agents [ Time Frame: Up to 4 years after Last Patient First Visit (LPFV) ]
Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment
Inclution 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 (ICF)
Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R):
Very high
High
Intermediate with at least ≥ 5% bone marrow blast
Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
Not eligible at the 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.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Signed informed consent must be obtained prior to participation in the study.
Age ≥ 18 years at the date of signing the informed consent form (ICF)
Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R):
Very high
High
Intermediate with at least ≥ 5% bone marrow blast
Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions
Not eligible at the 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.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria
Exclusion Criteria:
Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.
Previous first-line treatment for higher risk MDS with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.
History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).
Currently using or used within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.
Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
Live vaccine administered within 30 Days prior to randomization.
Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.
Previous first-line treatment for higher risk MDS with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.
History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).
Currently using or used within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.
Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
Live vaccine administered within 30 Days prior to randomization.
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
127 participants
