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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04150029




Registration number
NCT04150029
Ethics application status
Date submitted
22/10/2019
Date registered
4/11/2019

Titles & IDs
Public title
A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy
Scientific title
A Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy
Secondary ID [1] 0 0
2019-000439-14
Secondary ID [2] 0 0
CMBG453C12201
Universal Trial Number (UTN)
Trial acronym
STIMULUS-AML1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MBG453
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine

Experimental: MBG453+Venetoclax +Azacitidine - Patients will receive MBG453 in combination with Venetoclax and Azacitidine


Treatment: Drugs: MBG453
Solution for intravenous infusion

Treatment: Drugs: Venetoclax
Tablet for oral administration

Treatment: Drugs: Azacitidine
Solution for subcutaneous injection or intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (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 subjects achieving complete remission (CR)
Timepoint [2] 0 0
at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days)
Secondary outcome [1] 0 0
Percentage of subjects achieving a complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi)
Timepoint [1] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [2] 0 0
Time from date of first documented CR or CRi to the date of first documented relapse or death due to any cause
Timepoint [2] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [3] 0 0
Time from the date of the first documented CR to the date of first documented relapse or death due to any cause
Timepoint [3] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [4] 0 0
Time from start of treatment until death, relapse from CR, or treatment failure, whichever occurs first
Timepoint [4] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [5] 0 0
Time from start of treatment to death due to any cause (overall survival)
Timepoint [5] 0 0
date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment)
Secondary outcome [6] 0 0
Peak Serum Concentration (Cmax) MBG453
Timepoint [6] 0 0
Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
Secondary outcome [7] 0 0
Trough Serum Concentration (Cmin) MBG453
Timepoint [7] 0 0
Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months
Secondary outcome [8] 0 0
Trough Plasma Concentration (Cmin) Venetoclax
Timepoint [8] 0 0
Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
Secondary outcome [9] 0 0
Anti-drug Antibody (ADA) prevalence at baseline
Timepoint [9] 0 0
prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
Secondary outcome [10] 0 0
ADA prevalence on-treatment
Timepoint [10] 0 0
Throughout study until 150 day safety follow-up
Secondary outcome [11] 0 0
Percentage of MRD-negative subjects in the full study population and in subjects achieving CR or CRi
Timepoint [11] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [12] 0 0
Rate of subjects who achieve transfusion independence from baseline and while on treatment.
Timepoint [12] 0 0
from start of treatment up to 48 months from last patient first treatment
Secondary outcome [13] 0 0
Percentage of subjects achieving a complete remission (CR) or complete remission with partial hematologic blood count recovery (CRh)
Timepoint [13] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Secondary outcome [14] 0 0
Time from date of first documented CR or CRh to the date of first documented relapse or death due to any cause
Timepoint [14] 0 0
every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment

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. Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age =75, ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF = 50%, chronic stable Angina) , pulmonary comorbidity (DLCO = 65% or FEVI = 65%). moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN) , renal impairment (eGFR= 30 ml/min/1.73m^2 to 45 30 ml/min/1.73m^2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessement and approved by the Novartis Medical monitor)
4. .Not planned for hematopoietic stem-cell transplantation (HSCT)
5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3
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
2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
3. Current use or use within 14 days prior to randomization 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.
4. Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
5. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
6. Live vaccine administered within 30 Days prior to randomization

Other protocol-defined Inclusion/Exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/10/2024
Actual
Sample size
Target
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Paris 10
Country [15] 0 0
France
State/province [15] 0 0
Toulouse
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Leipzig
Country [18] 0 0
Italy
State/province [18] 0 0
MI
Country [19] 0 0
Italy
State/province [19] 0 0
RM
Country [20] 0 0
Japan
State/province [20] 0 0
Fukushima
Country [21] 0 0
Japan
State/province [21] 0 0
Yamagata
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seocho Gu
Country [23] 0 0
Spain
State/province [23] 0 0
Catalunya
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Taiwan
State/province [25] 0 0
Kaohsiung

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04150029