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
Tamibarotene plus azacitidine or placebo plus azacitidine.
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.
Primary outcome:
1. Proportion of Participants with Complete Remission (Time Frame - Up to 5 Years)
Secondary outcome:
1. Duration of Overall Survival (Time Frame - Up to 5 Years)
2. Proportion of Participants Who Achieve Transfusion Independence (Time Frame - Up to 5 Years)
3. Proportion of Participants Who Achieve Objective Response (Time Frame - Up to 5 Years)
4. Duration of Complete Response (Time Frame - Up to 5 Years)
5. Duration of Overall Response (Time Frame - Up to 5 Years)
6. Time to Complete Remission (Time Frame - Up to 5 Years)
7. Time to Initial Response (Time Frame - Up to 5 Years)
8. Duration of Event Free Survival (Time Frame - Up to 5 Years)
9. Change in Health-Related Quality of Life (HRQOL) as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 Scale (EORTC QLQ-30) (Time Frame - Up to 5 Years)
10. Change in HRQOL as assessed by the European Quality of Life 5 dimensions Scale (EuroQoL-5D) (Time Frame - Up to 5 Years)
11. Proportion of participants with Adverse Events and Serious Adverse Events (Time Frame - Up to 5 Years)
- Experimental: Tamibarotene + Azacitidine
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. - Placebo Comparator: Tamibarotene Matched Placebo + Azacitidine
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.
- Tamibarotene (SY-1425):
Administered as specified in the treatment arm - Placebo:
Administered as specified in the treatment arm - Azacitidine:
Administered as specified in the treatment arm
Quelle: ClinicalTrials.gov
