Tamibarotene + Venetoclax/Azacitidine for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Syros Pharmaceuticals

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults with newly diagnosed AML who can't start standard chemo due to age, health, or other issues. They must have a certain gene abnormality (RARA-positive) and not have had previous treatments for their leukemia except hydroxyurea.

Inclusion Criteria

My blood test before treatment showed I am RARA-positive.

Exclusion Criteria

I have not had specific treatments for AML, MDS, or other blood cancers before starting this trial, except for hydroxyurea.

I have acute promyelocytic leukemia (APL).

My acute myeloid leukemia has spread to my brain or spinal cord.

Participant Groups

The study tests Tamibarotene combined with Venetoclax and Azacitidine in patients with acute myeloid leukemia (AML). It targets those whose cancer has the RARA gene overexpression and are unsuitable for standard chemotherapy.

4Treatment groups

Experimental Treatment

Active Control

Group I: Part 3: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Part 2 participants treated with venetoclax/azacitidine who experience progressive disease, relapse after initial CR or CRi response, or treatment failure may begin subsequent treatment in Part 3, where tamibarotene will be added to their regimen.

Group II: Part 2: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination at the dose and regimen selected in Part 1.

Group III: Part 1: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 milligrams (mg)/square meter (m\^2) once daily, on Days 1 through 7 of each 28-day therapy cycle (per VIDAZA USPI). Alternative dosing of azacitidine (Days 1 through 5, 8, and 9) will be permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing is 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg twice daily (BID) orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene will only be administered to participants who have been confirmed as RARA-positive.

Group IV: Part 2: Venetoclax/AzacitidineActive Control2 Interventions

Participants will receive the venetoclax/azacitidine combination at the dose and regimen selected in Part 1.

Azacitidine is already approved in European Union, United States, Canada, Japan, Australia for the following indications:

🇪🇺 Approved in European Union as Vidaza for: