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Trial details
A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants
Current status:
Approved
|
Date registered:
06/06/2022
Trial version(s)
History: 21/04/2022
Current: 21/04/2022
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2022055033
Protocol number
CMBG453B12203
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Novartis Pharmaceuticals
Primary sponsor: Country of origin
Novartis Pharmaceuticals
Public title
A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants
Acronym
STIMULUS-MDS3
Scientific title
A Single-arm, Open-label, Phase II Study of Sabatolimab in Combination With Azacitidine and Venetoclax in Adult Participants With High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria
Acronym
STIMULUS-MDS3
Brief summary of the study: English
The purpose of the study is to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, is safe and has beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who are not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).
Brief summary of the study: Arabic
الغرض من الدراسة هو معرفة ما إذا كان الدواء الجديد ساباتوليماب عند إعطائه بالاشتراك مع أزاسيتيدين وفينيتوكلاكس، آمنًا وله آثار مفيدة لدى المشاركين الذين يعانون من متلازمة خلل التنسّج النقوي العالية الخطورة أو ذات الخطورة العالية جدًا غير المناسبين للعلاج الكيميائي المكثّف أو لزرع الخلايا الجذعيّة.
Health conditions/problem studied: Specify
Myelodysplastic Syndromes (MDS)
Interventions: Specify
- Drug: sabatolimab Sabatolimab will be administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2 and Expansion (Part 2)) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle. - Drug: azacitidine A standard dose of azacitidine will be given subcutaneously or intravenously every day for seven consecutive days on days 1-7 of a confirmed treatment cycle. In keeping with standard clinical practice, the alternative schedules for five consecutive days on days 1-5, followed by a two day break, then two consecutive days on days 8-9 will be permitted (alternative schedule). - Drug: venetoclax Venetoclax film-coated tablets will be administered at a dose of 400 mg orally or corresponding reduced dose for concomitant use with P-gp inhibitors or moderate or strong CYP3A4 inhibitors, once a day, from C1D1 to C1D14 during the treatment cycle. No ramp-up for venetoclax is necessary.
Key inclusion and exclusion criteria: 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- Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012): - Very high (> 6 points) - High (> 4.5-6 points) 4- Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017) 5- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
1- Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time 2- Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment 3- Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed. 4- Live vaccine administered within 30 days prior to start of treatment 5- Current use or use within 14 days prior to start of treatment 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 6- History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients 7- Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 4.5
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
N/A
Study design: Masking
Open (masking not used)
Study design: Control
N/A
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Other
Study design: Specify assignment
Sequential
IMP has market authorization
No
Name of IMP
Sabatolimab
Type of IMP
Immunological
Pharmaceutical class
humanized monoclonal antibody against human TIM-3
Therapeutic indication
Myelodysplastic Syndrome (MDS)
Therapeutic benefit
The purpose of the study is to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, is safe and has beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who are not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).
Biospecimen retention
Samples without DNA
Biospecimen description
Samples will be shipped to Labcorp laboratories
Target sample size
3
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
20/07/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
06/12/2025
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement 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.
Additional data URL
https://clinicaltrials.gov/ct2/show/record/NCT04812548?term=CMBG453B12203&draw=2&rank=1
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
ClinicalTrials.gov
NCT04812548
Sources of Monetary or Material Support
Name
Novartis Pharmaceuticals
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Ali
Bazarbachi
Beirut
Lebanon
+961 3 612434
bazarbac@aub.edu.lb
American University of Beirut Medical Center
Scientific
Hind
Khairallah
Beirut
Lebanon
+961 1 512002 ext 271
hind.khairallah@f attal.com.lb
Khalil Fattal et Fils
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut Medical Center
Ali Bazarbachi
Hematology/Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
17/03/2022
Fuad Zyiadeh
fz05@aub.edu.lb
+961 1 350 000 ext:5445
Countries of Recruitment
Name
Australia
Belgium
France
Germany
Greece
Hungary
Italy
Spain
United States of America
Lebanon
Health Conditions or Problems Studied
Condition
Code
Keyword
Myelodysplastic Syndrome
Myelodysplastic syndrome, unspecified (D46.9)
MDS
Interventions
Intervention
Description
Keyword
Informed consent, IMP administration, questionnaire, Lab tests
Informed consent, IMP administration, questionnaire, Lab tests
Informed consent, IMP administration, questionnaire, Lab tests
Primary Outcomes
Name
Time points
Measure
Incidence of dose limiting toxicities (DLTs) (Safety run-in patients only)
From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days)
Assessment of tolerability of MBG in combination with venetoclax and azacitidine
Percentage of participants (receiving 800mg sabatolimab) achieving complete remission (CR) per investigator assessment
Throughout study completion, up to 3 years
This endpoint will assess Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood.
Key Secondary Outcomes
Name
Time points
Measure
Percentage of subjects achieving a complete remission (CR) + morphologic complete remission (mCR): Safety run-in (Part 1) and Expansion (Part 2)
Throughout study completion, an average of 3 years
Assessing the durability of complete remission (CR) or morphologic complete remission (mCR) rate (defined as the proportion of participants with best overall response of either CR or mCR)
Overall Response Rate (ORR) of participants who achieved hematologic improvement (HI) or better as best response
Throughout study completion, an average of 3 years
The percentage of participants achieving [CR + mCR + partial remission (PR) + hematologic improvement (HI)], per modified IWG-MDS Cheson 2006 criteria
Percentage of participants who are RBC/platelets transfusion independent
Continuously collected from start of treatment up to 3 years from last patient first treatment
Improvement in red blood cells (RBC)/platelets transfusion independence as per IWG-MDS by dose level
Duration of transfusion independence
Continuously collected from start of treatment up to 3 years from last patient first treatment
Transfusion independence as per IWG-MDS by dose level
Peak Serum Concentration (Cmax) MBG453
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment
Maximal concentration of MBG453
Trough Serum Concentration (Cmin) MBG453
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment
Concentration of sabatolimab prior to next dosing or after end of treatment
Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment by dose level
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment
Immunogenicity of sabatolimab prior to sabatolimab exposure and during treatment
Duration of complete remission (CR)
Throughout study completion, an average of 3 years
Duration of CR is defined as time from first occurrence of CR to relapse from CR, progression or death due to any cause whichever occurs first
Time to complete remission(CR)/marrow complete remission (mCR)
Throughout study completion, an average of 3 years
Time to CR/mCR is defined as time from start of treatment to first occurrence of CR or mCR as per investigator assessment
Duration of CR/mCR
Throughout study completion, an average of 3 years
Duration of CR/mCR is defined as time from first occurrence of CR/mCR to relapse from CR, progression or death due to any cause whichever occurs first
Duration of response for participants who achieved hematologic improvement (HI) or better
Throughout study completion, an average of 3 years
The duration of response will be derived for participants treated with sabatolimab at the higher dose who achieve HI or better as per investigator assessment and is defined from the first occurrence of CR, mCR, PR or HI until relapse, progression or death due to any reason
Progression-Free Survival (PFS)
Throughout study completion, an average of 3 years
Time from start of treatment to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR or death due to any cause, whichever occurs first
Leukemia-Free Survival (LFS)
Throughout study completion, an average of 3 years
Time from start of treatment to transformation to acute leukemia
Event-Free Survival (EFS)
Throughout study completion, an average of 3 years
Time from start of treatment to lack of reaching CR within the first 6 cycles, relapse from CR or death due to any cause, whichever occurs first
Overall Survival (OS)
Date of start of treatment to date of death due to any reason (for up to 3 years from last patient first treatment)
Time from start of treatment to death due to any cause
Changes in fatigue
Throughout the Expansion Phase, an average of 3 years
Changes in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue for participants treated with sabatolimab at the higher dose of the expansion part only. Measurements are taken via scores from 0 (not at all) to 4 (very much). The higher the score, the better the Quality of Life.
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Initial submission and Import license
06/05/2022
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