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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04797780
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : May 16, 2023
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 (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 + Azacitidine Drug: Tamibarotene Matched Placebo + 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 : 190 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 : December 31, 2023
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 + Azacitidine

Tamibarotene will be administered at 6 mg twice per day (BID) (orally) each day on Days 8 through 28 of each 28-day treatment cycle (total daily dose of 12 mg).

Azacitidine will be administered at 75 mg/m2 (intravenously or subcutaneously) each day on Days 1 through 7 of each 28-day treatment cycle. If dosing on Days 6 and 7 is not possible due to logistical limitations, these doses may be delayed to Days 8 and 9. Tamibarotene/placebo is permitted to overlap with azacitidine on Days 8 through 9 of this alternative schedule.

Other Name: SY-1425
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: Tamibarotene Matched Placebo + Azacitidine

Tamibarotene matched placebo will be administered at twice per day (BID) (orally) each day on Days 8 through 28 of each 28-day treatment cycle.

Azacitidine will be administered at 75 mg/m2 (intravenously or subcutaneously) each day on Days 1 through 7 of each 28-day treatment cycle. If dosing on Days 6 and 7 is not possible due to logistical limitations, these doses may be delayed to Days 8 and 9. Tamibarotene/placebo is permitted to overlap with azacitidine on Days 8 through 9 of this alternative schedule.


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. Proportion of Participants Who Achieve Objective Response [ Time Frame: Up to 5 Years ]
  2. Duration of Event Free Survival [ Time Frame: Up to 5 Years ]
  3. Duration of Overall Survival [ Time Frame: Up to 5 Years ]
  4. Proportion of Participants Who Achieve Transfusion Independence [ Time Frame: Up to 5 Years ]
  5. Duration of Complete Response [ Time Frame: Up to 5 Years ]
  6. Duration of Overall Response [ Time Frame: Up to 5 Years ]
  7. Time to Complete Remission [ Time Frame: Up to 5 Years ]
  8. Time to Initial Response [ Time Frame: Up to 5 Years ]
  9. 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:

  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.
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 857-327-7269 SELECTMDS1@syros.com

Locations
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Sponsors and Collaborators
Syros Pharmaceuticals
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: May 16, 2023
Last Verified: May 2023
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