A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy (STIMULUS-AML1)

January 17, 2024 updated by: Novartis Pharmaceuticals

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 will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax.

Study Overview

Status

Active, not recruiting

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

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Novartis Investigative Site
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 1Z6
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Novartis Investigative Site
      • Paris 10, France, 75475
        • Novartis Investigative Site
      • Toulouse, France, 31059
        • Novartis Investigative Site
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Leipzig, Germany, 04103
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00133
        • Novartis Investigative Site
      • Yamagata, Japan, 990 9585
        • Novartis Investigative Site
    • Fukushima
      • Fukushima city, Fukushima, Japan, 960 1295
        • Novartis Investigative Site
    • Seocho Gu
      • Seoul, Seocho Gu, Korea, Republic of, 06591
        • Novartis Investigative Site
      • Madrid, Spain, 28009
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • Kaohsiung, Taiwan, 83301
        • Novartis Investigative Site
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • 25Uni of Alabama at Birmingham
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School Of Medicine .
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics Univ of Iowa
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute Dana Farber Cancer Int
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester Dept. of Mayo Clinic (2)
    • New York
      • New York, New York, United States, 10017
        • Memorial Sloan Kettering Dept. of MSKCC
      • New York, New York, United States, 10021
        • Weill Cornell Medicine NY-Presb .
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Insitute Carolinas Healthcare System
      • Durham, North Carolina, United States, 27710
        • Duke Univ Medical Center .
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Oncology and Hematology Associates PC Tennessee Oncology Chattanooga
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center/University of Texas MD Anderson
    • Utah
      • Salt Lake City, Utah, United States, 84112 0550
        • Huntsman Cancer Institute Univ of Utah .

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Age ≥ 18 years at the date of signing the informed consent form (ICF)
  3. 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)
  4. .Not planned for hematopoietic stem-cell transplantation (HSCT)
  5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclusion Criteria:

  1. Prior exposure to TIM-3 directed therapy
  2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
  3. 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.
  4. 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.
  5. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
  6. Live vaccine administered within 30 Days prior to randomization

Other protocol-defined Inclusion/Exclusion may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: MBG453+Venetoclax +Azacitidine
Patients will receive MBG453 in combination with Venetoclax and Azacitidine
Solution for intravenous infusion
Other Names:
  • Sabatolimab
Solution for subcutaneous injection or intravenous infusion
Tablet for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Assessment of tolerability of MBG in combination with venetoclax and azacitidine
From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days
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)
Assessing Complete Remission (CR) Rate (Safety run in (expansion dose Level only) + Expansion)
at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time to relapse from CR/CRi or death (relapse free survival), whichever occurs first
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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
Assessing the durability of complete remission (CR) by determining the Relapse Free Survival (RFS) in subjects who achieved CR, whichever occurs first
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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
Assessing event free survival (EFS).
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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)
Time to death due to any cause to assess overall survival
date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment)
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
Maximal concentration of MBG453
Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
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
Concentration of MBG453 prior to next dosing or after end of treatment
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
Time Frame: Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
Trough concentration of venetoclax on treatment
Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
Anti-drug Antibody (ADA) prevalence at baseline
Time Frame: prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
Immunogenicity to MBG453 prior to MBG453 exposure
prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
ADA prevalence on-treatment
Time Frame: Throughout study until 150 day safety follow-up
Immunogenicity to MBG453 on Treatment and after treatment
Throughout study until 150 day safety follow-up
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
Rate of MRD-negative subjects
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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
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
from start of treatment up to 48 months from last patient first treatment
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
Assessing the complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi) Rate
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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
Assessing the complete remission (CR) or complete remission with partial hematologic blood count recovery (CRh) Rate
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
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
Time to relapse from CR/CRh or death (relapse free survival), whichever occurs first
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2020

Primary Completion (Estimated)

March 13, 2026

Study Completion (Estimated)

March 13, 2026

Study Registration Dates

First Submitted

October 22, 2019

First Submitted That Met QC Criteria

October 31, 2019

First Posted (Actual)

November 4, 2019

Study Record Updates

Last Update Posted (Actual)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 17, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

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

Yes

Studies a U.S. FDA-regulated device product

No

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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