- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04150029
A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy (STIMULUS-AML1)
A Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax.
The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.
There will be an analyis of the CR rate, after all subjects have completed at least 12 cycles of treatment ( cycle =28Days) or discontinued earlier.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Victoria
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Clayton, Victoria, Australia, 3168
- Novartis Investigative Site
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1M9
- Novartis Investigative Site
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Ontario
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Toronto, Ontario, Canada, M5G 1Z6
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Novartis Investigative Site
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Paris 10, France, 75475
- Novartis Investigative Site
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Toulouse, France, 31059
- Novartis Investigative Site
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Berlin, Germany, 13353
- Novartis Investigative Site
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Leipzig, Germany, 04103
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20162
- Novartis Investigative Site
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RM
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Roma, RM, Italy, 00133
- Novartis Investigative Site
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Yamagata, Japan, 990 9585
- Novartis Investigative Site
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Fukushima
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Fukushima city, Fukushima, Japan, 960 1295
- Novartis Investigative Site
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Seocho Gu
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Seoul, Seocho Gu, Korea, Republic of, 06591
- Novartis Investigative Site
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Madrid, Spain, 28009
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08036
- Novartis Investigative Site
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Kaohsiung, Taiwan, 83301
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, United States, 35294
- 25Uni of Alabama at Birmingham
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School Of Medicine .
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics Univ of Iowa
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute Dana Farber Cancer Int
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Rochester Dept. of Mayo Clinic (2)
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New York
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New York, New York, United States, 10017
- Memorial Sloan Kettering Dept. of MSKCC
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New York, New York, United States, 10021
- Weill Cornell Medicine NY-Presb .
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Cancer Insitute Carolinas Healthcare System
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Durham, North Carolina, United States, 27710
- Duke Univ Medical Center .
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Tennessee
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Chattanooga, Tennessee, United States, 37404
- Chattanooga Oncology and Hematology Associates PC Tennessee Oncology Chattanooga
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center/University of Texas MD Anderson
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Utah
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Salt Lake City, Utah, United States, 84112 0550
- Huntsman Cancer Institute Univ of Utah .
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
- Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m^2 to 45 30 ml/min/1.73m^2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessement and approved by the Novartis Medical monitor)
- .Not planned for hematopoietic stem-cell transplantation (HSCT)
- .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3
Exclusion Criteria:
- Prior exposure to TIM-3 directed therapy
- History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
- Current use or use 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.
- Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
- Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
- Live vaccine administered within 30 Days prior to randomization
Other protocol-defined Inclusion/Exclusion may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: MBG453+Venetoclax +Azacitidine
Patients will receive MBG453 in combination with Venetoclax and Azacitidine
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Solution for intravenous infusion
Other Names:
Solution for subcutaneous injection or intravenous infusion
Tablet for oral administration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of dose limiting toxicities (Safety run-in patients only)
Time Frame: From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days
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Assessment of tolerability of MBG in combination with venetoclax and azacitidine
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From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days
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Percentage of subjects achieving complete remission (CR)
Time Frame: at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days)
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Assessing Complete Remission (CR) Rate (Safety run in (expansion dose Level only) + Expansion)
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at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time from date of first documented CR or CRi to the date of first documented relapse or death due to any cause
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time to relapse from CR/CRi or death (relapse free survival), whichever occurs first
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time from the date of the first documented CR to the date of first documented relapse or death due to any cause
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Assessing the durability of complete remission (CR) by determining the Relapse Free Survival (RFS) in subjects who achieved CR, whichever occurs first
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time from start of treatment until death, relapse from CR, or treatment failure, whichever occurs first
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Assessing event free survival (EFS).
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time from start of treatment to death due to any cause (overall survival)
Time Frame: date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment)
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Time to death due to any cause to assess overall survival
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date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment)
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Peak Serum Concentration (Cmax) MBG453
Time Frame: Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
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Maximal concentration of MBG453
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Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
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Trough Serum Concentration (Cmin) MBG453
Time Frame: Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months
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Concentration of MBG453 prior to next dosing or after end of treatment
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Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months
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Trough Plasma Concentration (Cmin) Venetoclax
Time Frame: Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
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Trough concentration of venetoclax on treatment
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Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
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Anti-drug Antibody (ADA) prevalence at baseline
Time Frame: prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
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Immunogenicity to MBG453 prior to MBG453 exposure
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prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
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ADA prevalence on-treatment
Time Frame: Throughout study until 150 day safety follow-up
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Immunogenicity to MBG453 on Treatment and after treatment
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Throughout study until 150 day safety follow-up
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Percentage of MRD-negative subjects in the full study population and in subjects achieving CR or CRi
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Rate of MRD-negative subjects
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Rate of subjects who achieve transfusion independence from baseline and while on treatment.
Time Frame: from start of treatment up to 48 months from last patient first treatment
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Percentage of subjects who are not dependent on blood transfusions for more than 8 weeks will be determined and related to the total number of patients participating to report percentage
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from start of treatment up to 48 months from last patient first treatment
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Percentage of subjects achieving a complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi)
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Assessing the complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi) Rate
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Percentage of subjects achieving a complete remission (CR) or complete remission with partial hematologic blood count recovery (CRh)
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Assessing the complete remission (CR) or complete remission with partial hematologic blood count recovery (CRh) Rate
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time from date of first documented CR or CRh to the date of first documented relapse or death due to any cause
Time Frame: every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Time to relapse from CR/CRh or death (relapse free survival), whichever occurs first
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every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CMBG453C12201
- 2019-000439-14 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan 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.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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