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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04812548




Registration number
NCT04812548
Ethics application status
Date submitted
23/02/2021
Date registered
23/03/2021

Titles & IDs
Public title
A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants
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
Secondary ID [1] 0 0
2020-003669-21
Secondary ID [2] 0 0
CMBG453B12203
Universal Trial Number (UTN)
Trial acronym
STIMULUS-MDS3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndrome (MDS) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - sabatolimab
Treatment: Drugs - azacitidine
Treatment: Drugs - venetoclax

Experimental: sabatolimab + azacitidine + venetoclax - Part 1: Safety run-in consisted of 2 subsequent cohorts of a lower dose (cohort 1) and a higher dose (cohort 2) of sabatolimab in combination with fixed dose of venetoclax and azacitidine.

Part 2 (did not start as recruitment was stopped in Part 1) Expansion was to enroll additional participants to further investigate the regimen including sabatolimab at the higher dose, azacitidine and venetoclax. Participants data from Part 1 and Part 2 treated with the higher dose was to have been combined to determine the complete remission rate.


Treatment: Drugs: sabatolimab
Sabatolimab was administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle. Cycle = 28 days

Treatment: Drugs: azacitidine
A standard dose of azacitidine was 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 was permitted (alternative schedule).

Treatment: Drugs: venetoclax
Venetoclax film-coated tablets was 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 was necessary.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Dose Limiting Toxicities (DLTs) - All Grades (Safety run-in Patients Only)
Timepoint [1] 0 0
From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days)
Primary outcome [2] 0 0
Percentage of Participants (Receiving 800mg Sabatolimab) Achieving Complete Remission (CR) Per Investigator Assessment
Timepoint [2] 0 0
up to approx. 23 months
Secondary outcome [1] 0 0
Percentage of Subjects Achieving a Complete Remission (CR) + Morphologic Complete Remission (mCR): Safety run-in (Part 1)
Timepoint [1] 0 0
up to approx. 23 months
Secondary outcome [2] 0 0
Overall Response Rate (ORR) of Participants Who Achieved Hematologic Improvement (HI) or Better as Best Response
Timepoint [2] 0 0
up to approx. 23 months
Secondary outcome [3] 0 0
Percentage of Participants Who Are RBC/Platelets Transfusion Independent
Timepoint [3] 0 0
up to approx. 23 months
Secondary outcome [4] 0 0
Duration of Transfusion Independence
Timepoint [4] 0 0
up to approx. 23 months
Secondary outcome [5] 0 0
Peak Serum Concentration (Cmax) of Sabatolimab
Timepoint [5] 0 0
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months
Secondary outcome [6] 0 0
Trough Serum Concentration (Cmin) Sabatolimab
Timepoint [6] 0 0
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months
Secondary outcome [7] 0 0
Anti-drug Antibody (ADA) Prevalence at Baseline and ADA Incidence On-treatment by Dose Level
Timepoint [7] 0 0
Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months
Secondary outcome [8] 0 0
Duration of Complete Remission (CR)
Timepoint [8] 0 0
up to approx. 23 months
Secondary outcome [9] 0 0
Time to Complete Remission(CR)/Marrow Complete Remission (mCR)
Timepoint [9] 0 0
up to approx. 23 months
Secondary outcome [10] 0 0
Duration of Complete Response (CR)/Marrow Complete Response (mCR)
Timepoint [10] 0 0
up to approx. 23 months
Secondary outcome [11] 0 0
Duration of Response for Participants Who Achieved Hematologic Improvement (HI) or Better
Timepoint [11] 0 0
up to approx. 23 months
Secondary outcome [12] 0 0
Progression-Free Survival (PFS)
Timepoint [12] 0 0
up to approx. 23 months
Secondary outcome [13] 0 0
Leukemia-Free Survival (LFS)
Timepoint [13] 0 0
up to approx. 23 months
Secondary outcome [14] 0 0
Event-Free Survival (EFS)
Timepoint [14] 0 0
up to approx. 23 months
Secondary outcome [15] 0 0
Overall Survival (OS)
Timepoint [15] 0 0
Date of start of treatment to date of death due to any reason, for up to approx. 23 months
Secondary outcome [16] 0 0
Changes in Fatigue (Part 2 - Expansion)
Timepoint [16] 0 0
throughout study until progressive disease, death or study discontinuation, approx. 3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/05/2023
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brasschaat
Country [2] 0 0
France
State/province [2] 0 0
Marseille
Country [3] 0 0
France
State/province [3] 0 0
Nice
Country [4] 0 0
Germany
State/province [4] 0 0
Duesseldorf
Country [5] 0 0
Germany
State/province [5] 0 0
Stuttgart
Country [6] 0 0
Greece
State/province [6] 0 0
Evros
Country [7] 0 0
Greece
State/province [7] 0 0
Patras
Country [8] 0 0
Hungary
State/province [8] 0 0
Nyiregyhaza
Country [9] 0 0
Italy
State/province [9] 0 0
GE
Country [10] 0 0
Spain
State/province [10] 0 0
Catalunya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04812548