STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS
- Conditions
- Myelodysplastic Syndrome (MDS)
- Interventions
- Registration Number
- NCT04878432
- Lead Sponsor
- 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))
- 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 12 months;
3. Extension phase for efficacy and/or survival status (up to 12 months after core phase)
4. 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
- 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.
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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.
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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.
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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).
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Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification (Arber et al 2016).
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History of organ transplant or allogenic hematopoietic stem cell transplant
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Participants with prior malignancy, except:
- Participants with history of lower risk MDS treated by supportive care (e.g. growth factors, TGF-beta agents) or untreated are eligible
- Participants with history of lower risk MDS who were treated adequately with lenalidomide and then failed are eligible
- 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.
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Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 3
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MBG453 (sabatolimab) + HMA INQOVI (oral decitabine) MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine)) MBG453 (sabatolimab) + HMA MBG453 MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine)) MBG453 (sabatolimab) + HMA Azacitidine MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine)) MBG453 (sabatolimab) + HMA Decitabine MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine))
- Primary Outcome Measures
Name Time Method Number of treatment emergent adverse events and serious adverse events Baseline up to approximately 12 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
Name Time Method Progression free survival in participants with intermediate, high or very high risk MDS Baseline, every 12 weeks up to approximately 12 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 12 months post LPFT
Duration of complete remission Baseline, every 12 weeks up to approximately 12 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
Overall Survival Baseline, every 12 weeks up to approximately 24 months Time from enrollment to death due to any cause
Percentage of participants with complete response, marrow complete response and/or partial response Baseline, every 12 weeks up to approximately 24 months Percentage of complete response, marrow complete response, and/or partial response according to IWG-MDS response criteria as per investigator assessment
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
Leukemia-free survival Baseline, every 12 weeks up to approximately 12 months Time from enrollment to \> 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause
Time to complete remission Baseline, every 12 weeks up to approximately 12 months Time from first treatment to the first documented complete remission
Percentage of participants with improvement in RBC/platelets transfusion independence Baseline, every 12 weeks up to approximately 12 months Transfusion independence is defined as less than 3 units of transfusion within any 8 consecutive weeks on study
Trial Locations
- Locations (15)
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
University Hospitals Of Cleveland
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Texas Oncology San Antonio USO
🇺🇸San Antonio, Texas, United States
Karmanos Cancer Institute Div.of Hematology/Oncology
🇺🇸Detroit, Michigan, United States
Tisch Hospital NYU Langone
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
SCRI-Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Uni Of TX MD Anderson Cancer Cntr
🇺🇸Houston, Texas, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Associates .
🇺🇸Tucson, Arizona, United States
Yale University School Of Medicine .
🇺🇸New Haven, Connecticut, United States
Advent Health Orlando
🇺🇸Orlando, Florida, United States
Uni of Massachusetts Medical Center
🇺🇸Worcester, Massachusetts, United States
University Of Michigan .
🇺🇸Ann Arbor, Michigan, United States