Leukemia SY-1425-202

Tamibarotene in Combination with Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-positive AML Who Are Ineligible for Standard Induction Therapy

Sponsor(s): Syros

Tamibarotene is being studied as a treatment for participants with a type of leukemia called acute myeloid leukemia, or AML for short. Tamibarotene is being studied as a treatment for participants with AML whose cancer has a specific genetic abnormality characterized by the overexpression of the retinoic acid receptor alpha (RARA) gene. This genetic profile is found in about 3 of every 10 people with AML.

During the trial, tamibarotene will be given with 2 other drugs that are already used together to treat people who have AML and who cannot start treatment with standard chemotherapy.

Inclusion Criteria:

  • All participants must have obtained a blood sample for RARA biomarker investigational assay testing prior to starting treatment on Cycle 1 Day 1. The results of the investigational biomarker assay for all participants must be confirmed as RARA-positive by Cycle 1 Day 8 to enroll (Part 1) or to be randomized (Part 2) in the study.
  • Participants must have newly diagnosed, previously untreated non-acute promyelocytic leukemia (APL) AML with a bone marrow or peripheral blood blast count ≥20% and must be unlikely to tolerate standard intensive chemotherapy at the time of Cycle 1 Day 1 Visit due to age, performance status, or comorbidities based on at least one of the following criteria:
    • age ≥75 years old, or
    • age <75 years old, with at least one of the following:
    • Eastern Cooperative Oncology Group (ECOG) performance status of 3
    • cardiac history of congestive heart failure (CHF) or documented ejection fraction (EF) ≤50%
    • pulmonary disease with diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume in one second (FEV1) ≤65%
    • creatinine clearance ≥30 milliliters (mL)/minute (min) to <45 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation
    • hepatic impairment with total bilirubin >1.5 to ≤3.0 * upper limit of normal (ULN)

Exclusion Criteria:

  • Participants that have Acute promyelocytic leukemia (APL).
  • Participants that have known active central nervous system involvement with AML.
  • Prior treatment (before Cycle 1 Day 1) for the diagnosis of Acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or antecedent hematologic malignancy with any hypomethylating agent, venetoclax, chemotherapy, or hematopoietic stem cell transplantation (HSCT), with the exception of prior treatment with hydroxyurea.

Location(s): Hartford Hospital, Hospital of Central Connecticut, Midstate Medical Center

Contact(s): Christopher Sampson--860-972-5026

Cancer Clinical Research Office