Status and phase
Conditions
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Study type
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Identifiers
About
A study of siremadlin in combination with venetoclax plus azacitidine in adult participants with AML who are ineligible for chemotherapy.
The primary purpose of this study was to assess whether siremadlin in combination with venetoclax plus azacitidine can enhance the clinical response in unfit AML patients without unacceptable levels of treatment-emergent toxicities.
Full description
The recommended dose of siremadlin in combination with venetoclax plus azacitidine will be determined to be explored further in the expansion phase and the preliminary efficacy in achieving Complete Remission (CR) will be evaluated in participants who responded sub-optimally to first-line venetoclax plus azacitidine treatment.
The study was planned to be conducted in two parts. The primary purpose of Part 1 (Safety Run- in) was to rule out excessive toxicity of siremadlin when administered in combination with venetoclax plus azacitidine while the primary purpose of Part 2 (Expansion) was to evaluate the preliminary efficacy of siremadlin when combined with venetoclax plus azacitidine in the respective patient population.
The study treatment (siremadlin in combination with venetoclax plus azacitidine) is administered in cycles with a planned duration of 28 days and will continue until the participants experience disease progression/relapse or unacceptable toxicity.
The initial enrollment plan and safety review was as follow:
In the safety run-(Part 1) 27 sites were open for recruitment with 28 patients screened and 14 patients enrolled.
After enrolling 14 patients (6 patients in Arm 1 and 8 patients in Arm 2), Novartis took the decision to put the enrollment in permanent halt and terminate the siremadlin program. For that reason, the enrollment in Part 2 (expansion phase) will not be open. The Novartis decision was not driven by any safety concerns.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age at the date of signing the informed consent form (ICF): Arm 1 and Arm 2: ≥ 18 years
Participants diagnosed with AML based on WHO 2016 classification (Arber et al 2016) who are ineligible for standard induction chemotherapy and: Arm 1 : have received at least 2 cycles and not more than 4 cycles of first-line venetoclax plus azacitidine treatment and have not achieved a CR, CRi, CRh or MLFS.
Arm 2 : newly diagnosed AML with adverse genetic risk stratification (according to ELN 2022) (except TP53 mutation positive participants).
Participant (in both arms) must be considered ineligible for standard of care intensive induction chemotherapy defined by the following:
Participants must have an ECOG performance status:
0 to 2 for participants ≥ 75 years of age. OR 0 to 3 for participants ≥ 18 to 74 years of age.
WBC < 25x109/L
AST and ALT ≤ 3 × ULN
Estimated Glomerular Filtration Rate (eGFR)≥ 60 mL/min/1.73 m2
Exclusion criteria
Other protocol-defined inclusion/exclusion criteria may apply at the end
Primary purpose
Allocation
Interventional model
Masking
14 participants in 2 patient groups
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Central trial contact
Novartis Pharmaceuticals; Novartis Pharmaceuticals
Data sourced from clinicaltrials.gov
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