STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04878432
Collaborator
(none)
90
19
1
36.5
4.7
0.1

Study Details

Study Description

Brief Summary

Main objective of this study is to describe and evaluate safety and efficacy of MBG453 (sabatolimab) in combination with FDA approved HMAs of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a single-arm, non- randomized, open label, phase II multi-center study of intravenous MBG453 (sabatolimab) added to FDA approved Hypomethylating agents of investigator's choice (IV/SC/ Oral) in adult participants with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria.

There are three separate periods of this study:
  1. Screening period (signing of written informed consent through Day 1);

  2. Core phase for 24 months (with post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later);

  3. Extension phase for efficacy and/or survival status (up to 36 months from last patient enrolling) (with post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US)
Actual Study Start Date :
Mar 17, 2022
Anticipated Primary Completion Date :
Jan 1, 2024
Anticipated Study Completion Date :
Mar 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: MBG453 (sabatolimab) + HMA

MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine))

Drug: MBG453
Solution for intravenous infusion
Other Names:
  • sabatolimab
  • Drug: Azacitidine
    Solution for subcutaneous injection or intravenous infusion

    Drug: Decitabine
    Solution for intravenous infusion

    Drug: INQOVI (oral decitabine)
    Tablet for oral administration

    Outcome Measures

    Primary Outcome Measures

    1. Number of treatment emergent adverse events and serious adverse events [Baseline up to approximately 36 months plus 30 - 150 day safety follow up dependent on HMA]

      Adverse events will be assessed at each visit. Any clinically significant laboratory value or vital sign determined by the investigator to meet the definition of an adverse event will be reported.

    Secondary Outcome Measures

    1. Complete remission (CR) rate according to International Working Group (IWG) for MDS (2006) * as per investigator assessment by 12 months. [Baseline, by 12 months]

      Complete remission with MBG453 (sabatolimab) in combination with HMAs (IV/SC/Oral) in participants with intermediate, high, or very high risk MDS by 12 months

    2. Progression free survival in participants with intermediate, high or very high risk MDS [Baseline, every 12 weeks up to approximately 36 months]

      Defined as time from enrollment to disease progression (including transformation to 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 by 24 months and during extension phase to 36 months post LPFV

    3. Overall Survival [Baseline, every 12 weeks up to approximately 36 months]

      Time from enrollment to death due to any cause

    4. Leukemia-free survival [Baseline, every 12 weeks up to approximately 36 months]

      Time from enrollment to > 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause

    5. Percentage of participants with complete response, marrow complete response and/or partial response [Baseline, every 12 weeks up to approximately 36 months]

      Percentage of complete response, marrow complete response, and/or partial response according to IWG-MDS response criteria as per investigator assessment

    6. Duration of complete remission [Baseline, every 12 weeks up to approximately 36 months]

      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

    7. Time to complete remission [Baseline, every 12 weeks up to approximately 36 months]

      Time from first treatment to the first documented complete remission

    8. Percentage of participants with improvement in RBC/platelets transfusion independence [Baseline, every 12 weeks up to approximately 36 months]

      Transfusion independence is defined as less than 3 units of transfusion within any 8 consecutive weeks on study

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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) primary or secondary 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). Note: MDS diagnosis history will be recorded in the CRF:

    • Very high (> 6 points)

    • High (> 4.5 - ≤ 6 points)

    • Intermediate (> 3 - ≤ 4.5 points)

    • Not suitable at the time of screening for immediate myeloablative/ chemotherapy or hematopoietic stem cell transplantation based on investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these).

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

    • AST and ALT ≤ 3 × upper limit of normal (ULN).

    • Total bilirubin ≤ 2 × ULN (except in the setting of isolated Gilbert syndrome).

    • Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min/1.73m2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory).

    • Patient is able to communicate with the investigator and has the ability to comply with the requirements of the study procedures.

    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 are allowed only if the last dose of the drug was administered more than 4 months prior to enrollment.

    • Previous treatment for intermediate, high or very high risk myelodysplastic syndromes (based on IPSS-R) with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine or INQOVI (oral decitabine) (patients who had up to 1 cycle of HMAs can be included). However, previous treatment with hydroxyurea is permitted.

    • Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification (Arber et al 2016).

    • Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification (Arber et al 2016).

    • History of organ transplant or allogenic hematopoietic stem cell transplant

    • Participants with prior malignancy, except:

    1. Participants with history of lower risk MDS treated by supportive care (e.g. growth factors, TGF-beta agents) or untreated are eligible

    2. Participants with history of lower risk MDS who were treated adequately with lenalidomide and then failed are eligible

    3. Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study. Participants who are receiving adjuvant therapy such as hormone therapy are eligible.

    • Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer and Research Centers Chandler Arizona United States 85224
    2 Arizona Oncology Associates Arizona Oncology Assoc PC Phoenix Arizona United States 85016
    3 Mayo Clinic Arizona Phoenix Arizona United States 85054
    4 Arizona Oncology Associates Tucson Arizona United States 85745
    5 Arizona Oncology Associates Tucson Arizona United States 85745
    6 SCRI- Colorado Blood Cancer Institute Denver Colorado United States 80218
    7 AdventHealth Orlando Orlando Florida United States 32803
    8 Illinois Cancer Care P.C. IL Cancer Specialists Peoria Illinois United States 61615-7828
    9 Illinois Cancer Care P.C. Peoria Illinois United States 61615-7828
    10 University of Massachusetts Medical Center Worcester Massachusetts United States 01655
    11 University of Michigan Ann Arbor Michigan United States 48109
    12 Karmanos Cancer Institute Div.of Hematology/Oncology Detroit Michigan United States 48201
    13 Tisch Hospital NYU Langone New York New York United States 10016
    14 Messino Cancer Centers Asheville North Carolina United States 28806
    15 University Hospitals of Cleveland Cleveland Ohio United States 44106
    16 Alliance Cancer Specialists USO Horsham Pennsylvania United States 19044
    17 Texas Oncology-Baylor USO Dallas Texas United States 75246
    18 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    19 Texas Oncology San Antonio USO San Antonio Texas United States 78240

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04878432
    Other Study ID Numbers:
    • CMBG453B1US01
    First Posted:
    May 7, 2021
    Last Update Posted:
    Jun 22, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 22, 2022