Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome

Syros Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Myelodysplastic Syndromes

Treatments: Drug: Placebo; Drug: Tamibarotene; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04797780

2020-004528-40 (EudraCT Number)

SY-1425-301

Details and patient eligibility

About

This study compares the efficacy of Tamibarotene in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (HR-MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms.

Full description

A subset of participants have MDS characterized by an overexpression of the RARA gene. A blood test will be used to identify participants with RARA-positive MDS. Assessment of the RARA biomarker for study eligibility will be done by collection of blood samples from potential study participants at the pre-screening visit and testing at a central laboratory. Participants who meet eligibility requirements will be randomized 2:1 to receive either Tamibarotene plus azacitidine or placebo plus azacitidine.

Enrollment: 246 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants must be RARA-positive based on the investigational assay.

• Participants must be newly diagnosed with HR-MDS as follows:

  • Diagnosis of MDS according to the World Health Organization (WHO) classification and classified by the Revised International Prognostic Scoring System (IPSS R) risk category as very high, high, or intermediate risk.

• Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.

Key Exclusion Criteria:

• Participants are suitable for and agree to undergo allogeneic hematopoietic stem cell transplant (HSCT) at the time of screening.

  • Participants who need treatment prior to stem cell transplant can receive treatment on this study and stop the study treatment when they are ready to proceed to transplant.

• Participants who received prior treatment for MDS with any hypomethylating agent, lenalidomide, chemotherapy or allogeneic HSCT.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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246 participants in 2 patient groups, including a placebo group

Tamibarotene + Azacitidine

Experimental group

Description:

Tamibarotene: 6 mg administered orally twice per day (BID) on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m\^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.

Treatment:

Drug: Azacitidine

Drug: Tamibarotene

Tamibarotene Matched Placebo + Azacitidine

Placebo Comparator group

Description:

Placebo: Tamibarotene-matching tablets administered orally BID on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m\^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.

Treatment:

Drug: Azacitidine

Drug: Placebo