Description:
This study compares the efficacy of SY-1425 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 (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.
Title
- Brief Title: SY-1425 Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome
- Official Title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of SY-1425 Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, RARA-positive Adult Patients With Higher-risk Myelodysplastic Syndrome
Clinical Trial IDs
- ORG STUDY ID:
SY-1425-301
- SECONDARY ID:
2020-004528-40
- NCT ID:
NCT04797780
Conditions
- Myelodysplastic Syndromes
Interventions
| Drug | Synonyms | Arms |
|---|
| SY-1425 + Azacitidine | Tamibarotene | SY-1425 + Azacitidine |
| SY-1425 Matched Placebo + Azacitidine | | SY-1425 Matched Placebo + Azacitidine |
Purpose
This study compares the efficacy of SY-1425 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 (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.
Detailed 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
SY-1425 plus azacitidine or placebo plus azacitidine.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| SY-1425 + Azacitidine | Experimental | SY-1425: 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. | |
| SY-1425 Matched Placebo + Azacitidine | Placebo Comparator | Placebo: SY-1425-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. | - SY-1425 Matched Placebo + Azacitidine
|
Eligibility Criteria
Key Inclusion Criteria:
1. Participants must be at least 18 years old at the time of signing of an informed
consent.
2. Participants must be RARA-positive based on the investigational assay.
3. Participants must be newly diagnosed with HR-MDS as follows:
Diagnosis of MDS according to the World Health Organization (WHO) classification
(Arber 2016) and classified by the Revised International Prognostic Scoring System
(IPSS R) risk category as very high, high, or intermediate risk.
4. Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of
≤2.
Key Exclusion Criteria:
1. Participants are suitable for and agree to undergo allogeneic HSCT at the time of
Screening.
2. Participants who received prior treatment for MDS with any hypomethylating agent,
chemotherapy or allogeneic HSCT.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Proportion of Participants with Complete Remission |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Proportion of Participants Who Achieve Objective Response |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Event Free Survival |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Overall Survival |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of Participants Who Achieve Transfusion Independence |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Complete Response |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Overall Response |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Time to Complete Remission |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Time to Initial Response |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of participants with Adverse Events and Serious Adverse Events |
| Time Frame: | Up to 5 Years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Syros Pharmaceuticals |
Trial Keywords
- Higher-Risk
- Retinoic Acid Receptor Alpha (RARA) positive
- Newly Diagnosed
- Myelodysplastic Syndromes
Last Updated
August 25, 2021
