A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy (STIMULUS-AML1)

  • STATUS
    Recruiting
  • End date
    Mar 10, 2026
  • participants needed
    86
  • sponsor
    Novartis Pharmaceuticals
Send
Updated on 11 August 2022
See if I qualify
cell transplantation
azacitidine
venetoclax

Summary

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax.

Description

The purpose of the current study is to assess clinical effects of MBG453 in combination with hypomethylating agents (HMA) (azacitidine or decitabine) in adult subjects with International Prognostic Scoring System (IPSS-R) intermediate, high, very high risk MDS.

The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax.

The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.

There will be one analysis of the CR rate, 7 months after the last randomized subject. PFS will not be tested at this time point.

A maximum of two analyses will be performed for PFS. A PFS interim analysis will be scheduled when approximately 81 PFS events (after 75% of the planned target PFS events with an option to stop for efficacy) have been documented, expected to occur approximately 28 months after the first subject randomized. If PFS is not statistically significant at the IA, the study will continue until the final PFS analysis.

The final PFS analysis will be performed after observing approximately 108 PFS events (or at the latest at 4 years after the last subject is randomized) expected to occur approximately 51 months after the first subject randomized.

Details
Condition Acute Myeloid Leukemia
Treatment Azacitidine, venetoclax, MBG453
Clinical Study IdentifierNCT04150029
SponsorNovartis Pharmaceuticals
Last Modified on11 August 2022

Eligibility

 Yes No Not Sure

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)
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)
Not planned for hematopoietic stem-cell transplantation (HSCT)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclusion Criteria

Prior exposure to TIM-3 directed therapy
History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
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
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
Active autoimmune disease requiring systemic therapy (e.g.corticosteroids)
Live vaccine administered within 30 Days prior to randomization
Other protocol-defined Inclusion/Exclusion may apply
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

cell transplantation
azacitidine
venetoclax

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name
Edit Delete

Added by • 

 • 

Private

Edit Delete

Reply by • • Private
Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note