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A Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Chemotherapy.

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Brief Summary

A study of siremadlin in combination with venetoclax plus azacitidine in adult participants with AML who are ineligible for chemotherapy.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
99 Years

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
  1. (except TP53 mutation positive participants).
  • Participant must be considered ineligible for standard of care intensive induction chemotherapy defined by the following:
    • 75 years of age; OR
    • 18 to 74 years of age with at least one of the following co-morbidities: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; Cardiac history of congestive heart failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; DLCO ≤ 65% or FEV1 ≤ 65%.
  • 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:

  • Prior exposure to MDM2-inhibitor therapy at any time.
  • Participants with TP53 mutation positive, as defined by local TP53 testing.
  • Participants with del17p.
  • Participants with AML-M3 / APL (Acute promyelocytic leukemia) with PML-RARA (Promyelocytic leukemia/retinoic acid receptor alpha) or with AML secondary to Down's syndrome.
  • Participants treated with FLT3 inhibitors
  • Participants who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A4 inducers during the entire study
  • Participants who require treatment with substrates of CYP3A4/5 with a narrow therapeutic index.

Other protocol-defined inclusion/exclusion criteria may apply at the end

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Study Stats
Protocol No.
22-000184
Category
Hematology-Oncology
Oncology
Contact
Bruck Habtemariam
Location
  • UCLA Westwood
For Providers
NCT No.
NCT05155709
For detailed technical eligibility, visit ClinicalTrials.gov.