Acute Myeloid Leukemia Clinical Trial
A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy
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.
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.
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
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.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 28 Locations for this study
Birmingham Alabama, 35294, United States
New Haven Connecticut, 06520, United States
Iowa City Iowa, 52242, United States
Boston Massachusetts, 02215, United States
Rochester Minnesota, 55905, United States
New York New York, 10017, United States
New York New York, 10021, United States
Charlotte North Carolina, 28204, United States
Durham North Carolina, 27710, United States
Chattanooga Tennessee, 37404, United States
Houston Texas, 77030, United States
Salt Lake City Utah, 84112, United States
Clayton Victoria, 3168, Australia
Vancouver British Columbia, V5Z 1, Canada
Toronto Ontario, M5G 1, Canada
Montreal Quebec, H3T 1, Canada
Paris Cedex 10 , 75475, France
Toulouse , 31059, France
Berlin , 13353, Germany
Leipzig , 04103, Germany
Milano MI, 20162, Italy
Roma RM, 00133, Italy
Fukushima city Fukushima, 960 1, Japan
Yamagata , 990 9, Japan
Seoul Seocho Gu, 06591, Korea, Republic of
Barcelona Catalunya, 08036, Spain
Madrid , 28009, Spain
Kaohsiung City , 83301, Taiwan
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.