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

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ClinicalTrials.gov Identifier: NCT04797780
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : March 13, 2024
Sponsor:
Information provided by (Responsible Party):
Syros Pharmaceuticals

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Tamibarotene Drug: Placebo Drug: Azacitidine Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Tamibarotene Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, Adult Patients Selected for RARA-positive Higher-risk Myelodysplastic Syndrome (SELECT MDS-1)
Actual Study Start Date : February 8, 2021
Estimated Primary Completion Date : November 15, 2024
Estimated Study Completion Date : February 8, 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Azacitidine

Arms and Interventions
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Arm Intervention/treatment
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.

 Drug: Tamibarotene
Administered as specified in the treatment arm
Other Name: SY-1425

Drug: Azacitidine
Administered as specified in the treatment arm
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.

 Drug: Placebo
Administered as specified in the treatment arm

Drug: Azacitidine
Administered as specified in the treatment arm


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of Participants with Complete Remission [ Time Frame: Up to 5 Years ]

Secondary Outcome Measures :
  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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04797780


Contacts
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Contact: Clinical Trial Manager 617-674-9069 SELECTMDS1@syros.com

Locations
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Sponsors and Collaborators
Syros Pharmaceuticals
Investigators
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Study Director: Medical Director Syros Pharmaceuticals Inc.
More Information
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Responsible Party: Syros Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04797780    
Other Study ID Numbers: SY-1425-301
2020-004528-40 ( EudraCT Number )
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: March 13, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Syros Pharmaceuticals:
Higher-Risk
Retinoic Acid Receptor Alpha (RARA) positive
Newly Diagnosed
Myelodysplastic Syndromes
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
 Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors