Acute Myeloid LeukemiaPhase 2STIMULUS-AML1NCT04150029
A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy
A Phase 2 study testing MBG453, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia, run by Novartis Pharmaceuticals at 28 sites in 10 countries.
Trial summary
This trial seeked to extend the preliminary findings of efficacy by evaluating MBG453 in combination with hypomethylating agents (HMA) and also Bcl-2 inhibitor venetoclax. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- MBG453, Venetoclax and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 28 sitesin 10 countries
- Study dates
- 1 Sep 2020to 25 Oct 2024
- Phase
- Phase 2
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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
Who cannot join
- 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
Trial locations and contacts
28 sites in 10 countries.
28 sites in 10 countries
United States12 sites
25Uni of Alabama at Birmingham
Birmingham, Alabama, 35294
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Levine Cancer Insitute Carolinas Healthcare System
Charlotte, North Carolina, 28204
Chattanooga Onc And Hem Assoc PC
Chattanooga, Tennessee, 37404
Duke Univ Medical Center
Durham, North Carolina, 27710
MD Anderson Cancer Center University of Texas
Houston, Texas, 77030
Uni Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242
Yale University School Of Medicine
New Haven, Connecticut, 06520
Memorial Sloan Kettering
New York, New York, 10017
Weill Cornell Medicine NY-Presb
New York, New York, 10021
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Huntsman Cancer Institute Univ of Utah
Salt Lake City, Utah, 84112 0550
Canada3 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1M9
France2 sites
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Toulouse, 31059
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Leipzig, Saxony, 04103
Italy2 sites
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Roma, RM, 00133
Japan2 sites
Novartis Investigative Site
Fukushima, Fukushima, 960 1295
Novartis Investigative Site
Yamagata, Yamagata, 990 9585
Spain2 sites
Novartis Investigative Site
Barcelona, 08036
Novartis Investigative Site
Madrid, 28009
About this study
Official title: 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
This trial seeked to extend the preliminary findings of efficacy by evaluating MBG453 in combination with hypomethylating agents (HMA) and also Bcl-2 inhibitor venetoclax.
Read the detailed description
The primary purpose of Part 1 (Safety Run-in) was 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) was to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who were not suitable for treatment with intensive chemotherapy.
Originally, there was an analysis planned of the complete response (CR) rate, after all subjects had completed at least 12 cycles of treatment (each cycle = 28 Days) or discontinued earlier. As Novartis decided to end the development of this compound, this primary analysis was skipped and only the final study analysis presented here. At the final analysis timepoint, there was only 1 patient who didn't completed the 12 cycles of treatment or discontinued earlier.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- MBG453, Venetoclax, Azacitidine
- Keywords
- MBG453, Venetoclax, Azacitidine, Phase 2, AML, Acute myeloid Leukemia, Sabatolimab
- 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.
MBG453Drug
Also called Sabatolimab
Solution for intravenous infusion
VenetoclaxDrug
Tablet for oral administration
AzacitidineDrug
Solution for subcutaneous injection or intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| MBG453+Venetoclax +Azacitidine | Experimental | Participants received MBG453 in combination with Venetoclax and Azacitidine Receives: Drug: MBG453; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities (DLT)(Safety run-in Patients Only)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibily related to MBG453 as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets any of the criteria as per protolcol.
Measured: From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days
Percentage of Participants Achieving Complete Remission (CR) (CR Rate)
CR rate is defined as the percentage of participants achieving a complete remission (CR) as per investigator assessment (based on IWG Cheson et al 2003, ELN 2017 Dohner et al 2017).
Measured: approx. 31 months
Secondary outcomes (14)
Measurable Residual Disease (MRD) - Negativity Rate: Full Study Population
MRD negativity rate was defined as the percentage of participants with MRD negativity, which was defined as an MRD negative sample (frequency of LAIP below 0.1%, as determined by Multi-parameter Flow Cytometry-Measurable residual disease (MFC-MRD) at Central Lab) in participant with remission (i.e., CR or CRi) as per investigator assessment (based on IWG Cheson et al 2003, ELN 2017 Dohner et al 2017). MRD-negative response was required to be observed at or after morphological remission, and prior to relapse or disease progression.
Measured: approx. 31 months
Measurable Residual Disease (MRD) - Negativity Rate in Participants With Best Overall Response (BOR) of CR/CRi and Evaluable MRD
MRD negativity rate was defined as the percentage of participants with MRD negativity, which was defined as an MRD negative sample (frequency of LAIP below 0.1%, as determined by Multi-parameter Flow Cytometry-Measurable residual disease (MFC-MRD) at Central Lab) in participant with remission (i.e., CR or CRi) as per investigator assessment (based on IWG Cheson et al 2003, ELN 2017 Dohner et al 2017). MRD-negative response was required to be observed at or after morphological remission, and prior to relapse or disease progression.
Measured: approx. 31 months
Duration of Complete Remission (CR)
The duration of CR is defined as the time from first achievement of CR to the first documented relapse or progressive disease or death due to any cause, whichever occurs first. The response assessment is as per investigator assessment based on IWG (Cheson et al 2003) and ELN 2017 (Dohner et al 2017).
Measured: approx. 31 months
Percentage of Participants Achieving a Complete Remission (CR) or Complete Remission With Incomplete Hematologic Blood Count Recovery (CRi) (CR/CRi Rate)
CR/CRi rate is defined as the percentage pf participants with best overall response of either complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) as per investigator assessment (based on IWG (Cheson et al 2003) and ELN 2017 (Dohner et al 2017)).
Measured: approx. 31 months
The Duration of Complete Remission (CR)/Complete Remission With Incomplete Blood Count Recovery (CRi)
The duration of CR/CRi is defined as the time from first achievement of CR or CRi to the first documented relapse or progressive disease or death due to any cause, whichever occurs first. The response assessment is as per investigator assessment based on IWG (Cheson et al 2003) and ELN 2017 (Dohner et al 2017).
Measured: approx. 31 months
Percentage of Participants Achieving a Complete Remission (CR) or Complete Remission With Partial Hematologic Blood Count Recovery (CRh) (CR/CRh Rate)
CR/CRh rate is defined as the percentage of participants with best overall response of either complete remission (CR) or complete remission with partial hematologic recovery (CRh) as per derivation based on ELN 2022 (Döhner et al 2022).
Measured: approx. 31 months
Duration of CR/CRh
The duration of CR/CRh is defined as the time from date of first documented CR or CRh to the date of first documented relapse or death due to any cause, whichever occurs first. The response assessment is as per derivation based on ELN 2022 (Döhner et al 2022).
Measured: approx. 31 months
Event Free Survival (EFS)
EFS is the time from start of treatment until death due to any cause, relapse from complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), or treatment failure, whichever occurs first. Treatment failure was defined as lack of reaching CR until Cycle 8 Day 1 or earlier permanent discontinuation from study without reaching CR, the time to treatment failure was then set to Day 1.
Measured: approx. 31 months
Overall Survival (OS)
OS is the time from start of treatment to death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date).
Measured: approx. 31 months
Peak Serum Concentration (Cmax) of MBG453
Cmax is the maximal concentration of MBG453.
Measured: Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
Trough Serum Concentration (Cmin) MBG453
Cmin is the minimum concentration of MBG453 (i.e., prior to the next dosing).
Measured: Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months
Trough Plasma Concentration (Cmin) Venetoclax
Trough concentration of venetoclax on treatment
Measured: 0 hr (Pre-dose) of Day 8 of Cycle 1, 3 and 6 ; Cycle =28 days
Anti-drug Antibody (ADA) Prevalence at Baseline and ADA Positive Participants On-treatment
Immunogenicity (IG) to MBG453 prior to MBG453 exposure. ADA prevalence (i.e., ADA-positive samples) is the number of ADA-positive samples among the number of participants with a non-missing sample.
Measured: at baseline, up to 150 days after last treatment, approx. 24 months
Rate of Participants Who Achieved Transfusion Independence From Baseline and While on Treatment
Percentage of participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks.
Measured: approx. 31 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start1 Sep 2020
- Primary completion25 Oct 2024
- Study completion25 Oct 2024
Why it stopped: Novartis made a decision to early terminate the sabatolimab clinical development program, including the CMBG453C12201 trial, following the negative results from other 2 trials.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Sequential
- Model description
- safety -run -in with escalating dose of MBG453 followed by expansion
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04150029
- Sponsor's protocol ID
- CMBG453C12201
- Other IDs
- 2019-000439-14, 2019
- Acronym
- STIMULUS-AML1
- Status last verified
- Dec 2025
- First submitted
- 22 Oct 2019
- Last updated
- 13 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.