Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Gary Schiller, MD (ucla)

Description

Summary

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.

Official Title

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

Details

This study consists of 3 parts. In Part 1, the safety, tolerability, and pharmacokinetic (PK) evaluation of tamibarotene/venetoclax/azacitidine combination will inform the appropriate tamibarotene dose to be combined with the standard of care (SOC) venetoclax/azacitidine in Part 2 and Part 3. In Part 2, participants will be randomized 1:1 to receive either tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine to compare the clinical activity of the 2 combinations. In Part 3, tamibarotene will be added to the venetoclax/azacytidine regimen of a subset of Part 2 participants who experience progressive disease, relapse after initial complete remission (CR) or CR with incomplete blood count recovery (CRi) response, or treatment failure.

Keywords

Acute Myeloid Leukemia, Azacitidine, Venetoclax, Tamibarotene, Tamibarotene/Venetoclax/Azacitidine, Venetoclax/Azacitidine

Eligibility

For people ages 18 years and up

Note: all inclusion/exclusion criteria should be met prior to the first dose of venetoclax/azacitidine on Cycle 1 Day 1 with the exception of the RARA-biomarker test result referenced in inclusion criterion 2, which should be positive by Cycle 1 Day 8 to continue treatment on study.

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)
  • any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy, and reviewed and approved by the sponsor.

Exclusion Criteria:

  • Participants have APL.
  • Participants have known active central nervous system involvement with AML.
  • Prior treatment (before Cycle 1 Day 1) for the diagnosis of 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.

Locations

  • UCLA Medical Center Division of Hematology/Oncology accepting new patients
    Los Angeles California 90095 United States
  • City of Hope accepting new patients
    Duarte California 91010 United States

Lead Scientist at UC Cancer

  • Gary Schiller, MD (ucla)
    Professor-in-Residence, Medicine. Authored (or co-authored) 129 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Syros Pharmaceuticals
ID
NCT04905407
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 95 study participants
Last Updated