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

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ClinicalTrials.gov Identifier: NCT04878432
Recruitment Status : Recruiting
First Posted : May 7, 2021
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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
Myelodysplastic Syndrome (MDS) Drug: MBG453 Drug: Azacitidine Drug: Decitabine Drug: INQOVI (oral decitabine) 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).

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 17, 2022
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Decitabine

Arm Intervention/treatment
Experimental: MBG453 (sabatolimab) + HMA
MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine))
Drug: MBG453
Solution for intravenous infusion
Other Name: sabatolimab

Drug: Azacitidine
Solution for subcutaneous injection or intravenous infusion

Drug: Decitabine
Solution for intravenous infusion

Drug: INQOVI (oral decitabine)
Tablet for oral administration




Primary Outcome Measures :
  1. Number of treatment emergent adverse events and serious adverse events [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, every 12 weeks up to approximately 36 months ]
    Time from enrollment to death due to any cause

  4. Leukemia-free survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04878432


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04878432    
Other Study ID Numbers: CMBG453B1US01
First Posted: May 7, 2021    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 review 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 availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
sabatolimab
phase II
MBG453
TIM-3
decitabine
azacitidine
oral decitabine
INQOVI
myelodysplastic syndrome (MDS)
adult
MDS
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors