Tamibarotene + Venetoclax/Azacitidine for Acute Myeloid Leukemia

Recruiting at 30 trial locations

Overseen By Galina Craig

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Syros Pharmaceuticals

Must not be taking: Hypomethylating agents, Chemotherapy

Disqualifiers: APL, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

66 Participants Needed

What You Need to Know Before You Apply

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.

Who Is on the Research Team?

Michael Kelly Executive Medical Director, MD

Principal Investigator

Syros Pharmaceuticals

Are You a Good Fit for This Trial?

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

I have a new AML diagnosis, haven't been treated, and can't handle strong chemotherapy.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety and Dose Evaluation

Evaluation of safety, tolerability, and pharmacokinetics of tamibarotene/venetoclax/azacitidine combination to determine appropriate dosing

28 days per cycle

Multiple visits per cycle

Part 2: Randomized Treatment

Participants are randomized to receive either tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine to compare clinical activity

28 days per cycle, up to 3 years

Multiple visits per cycle

Part 3: Treatment for Progressive Disease

Tamibarotene is added to the regimen for participants experiencing progressive disease, relapse, or treatment failure

28 days per cycle, up to 3 years

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Tamibarotene
• Venetoclax

Trial Overview 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.

How Is the Trial Designed?

Group I: Part 3: Tamibarotene/Venetoclax/Azacitidine Experimental Treatment 3 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/Azacitidine Experimental Treatment 3 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/Azacitidine Experimental Treatment 3 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/Azacitidine Active Control 2 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 for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Syros Pharmaceuticals

Lead Sponsor

Trials

6

Recruited

1,000+