Go back to trials list
Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-positive AML Who Are Ineligible for Standard Induction Therapy
Description
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.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
Trial Eligibility
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.
Study Info
Organization
Syros Pharmaceuticals
Primary Outcome
Part 1: Number of Participants With Adverse Events
Interventions
Locations Recruiting
City of Hope
United States, California, Duarte
UCLA Medical Center Division of Hematology/Oncology
United States, California, Los Angeles
University of Colorado
United States, Colorado, Denver
Sarah Cannon Research Institute at Colorado Blood Cancer Institute
United States, Colorado, Denver
Hartford HealthCare
United States, Connecticut, Hartford
Interested in joining this trial?
Our dedicated patient navigators are here to guide you through the validation and enrollment process with ease.
![newsletter icon](https://static.healthtree.org/icons/newsletter-icon.png)
Get the latest thought leadership on your Acute Myeloid Leukemia delivered straight to your inbox
Subscribe to the weekly newsletter for news, stories, clinical trial updates, and helpful resources and events with cancer experts.
Thanks to our HealthTree Community for Acute Myeloid Leukemia Sponsors:
![Abbvie](https://firebasestorage.googleapis.com/v0/b/healthtree-production.appspot.com/o/gallery%2Fpublic%2Fabbvie%20bigger_c5e4f4af-fb3c-45ca-b9f0-831fb4c5f968.jpeg?alt=media)
![Astellas Pharma](https://firebasestorage.googleapis.com/v0/b/healthtree-production.appspot.com/o/university%2Fpublic%2Fshared%2Fastellas%20fo%20realz-100_8fd8c5cb-3421-4cfd-8aa6-07a70f67acf7.jpg?alt=media)
![Servier](https://firebasestorage.googleapis.com/v0/b/healthtree-production.appspot.com/o/gallery%2Fpublic%2Fservier_6f4f6f05-7255-45f8-8f3d-a07651617cbe.png?alt=media)