- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04996030
A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia
An Open-label Phase 1 Study to Evaluate Pharmacokinetics, Safety, and Tolerability of SY-2101 in Adult Patients With Acute Promyelocytic Leukemia
SY-2101 is being studied as a treatment for participants with a type of leukemia called acute promyelocytic leukemia (APL). SY-2101 is an oral formulation of a drug called arsenic trioxide (ATO). ATO is already used to treat APL in a formulation that is given as an intravenous (IV) infusion (through a needle in the arm). SY-2101 is a formulation of ATO that is taken orally (by mouth).
This trial will include participants with APL in remission, who are receiving standard of care (SOC) treatment with all-trans-retinoic acid (ATRA) and IV ATO, during the consolidation phase of chemotherapy or within the past 6 months. The participants in this trial will receive continued treatment with ATO and ATRA to help keep their cancer from coming back. There will be some weeks when participants receive IV ATO and others when they receive SY-2101 (ATO taken orally). Participants with high-risk APL may be eligible for part 1 or 4 of the study for the 6 months following completion of their standard of care ATRA and ATO treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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Illinois
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Chicago, Illinois, United States, 60208
- Northwestern Memorial Hospital
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Maryland
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Baltimore, Maryland, United States, 21287
- John Hopkins University
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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New York
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New York, New York, United States, 10065
- Weill Cornell Medical College
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Hillman Cancer Center
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
- Participants must have a diagnosis of APL characterized by the presence of the t(15;17) translocation or PML/RARA gene expression via reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), or cytogenetics. Participants with low-risk APL may be eligible for all parts of this study; participants with high-risk APL are only eligible for the single-dose modules if they have completed a treatment regimen that included ATO within 6 months prior to the Screening Visit.
- Participants must have received ATO plus ATRA induction therapy and must have received or be eligible and planning to receive consolidation therapy with ATO plus ATRA in alignment with National Comprehensive Cancer Network (NCCN) guidelines for low-risk APL prior to their enrollment in the study; or participants must have completed a treatment regimen that included ATO within 6 months prior to the Screening Visit.
- Participants must be able to tolerate full dose ATO per NCCN guidelines.
- Participants must be in morphological complete remission (CR) at the end of induction.
- Participants must have a serum or high-sensitivity urine pregnancy test (for females of childbearing potential) that is negative at the Screening Visit and immediately prior to initiation of study treatment (first dose of study drug).
Key Exclusion Criteria:
- Participants who have demonstrated relapse and therefore are not eligible for further consolidation.
- Participants currently receiving treatment for a non-APL malignancy (not including basal cell carcinoma, non-melanoma skin cancer, cervical carcinoma in situ, or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit.
- Participants with an active, life-threatening, or clinically-significant uncontrolled systemic infection requiring hospitalization.
- Immunocompromised participants with increased risk of opportunistic infections, including known human immunodeficiency virus (HIV)-positive participants with cluster of differentiation 4 (CD4) counts ≤350 cells/millimeters (mm^3) or history of opportunistic infection in the last 12 months.
- Participants with a known active or chronic hepatitis B or active hepatitis C virus (HCV) infection. Participants with a history of HCV infection who have completed curative therapy for HCV at least 12 weeks before the Screening Visit and have a documented undetectable viral load at the Screening Visit are eligible for enrollment.
- Participants who have not adequately recovered from a major surgery within 4 weeks of starting study drug administration.
- Participants who received any other investigational agents within 4 weeks of the Screening Visit or <5 half-lives since completion of previous investigational therapy have elapsed, whichever is shorter.
- Participants who have a hypersensitivity to arsenic.
- Participants who have experienced the following Grade ≥3 non-hematologic toxicities associated with ATO administration: QT prolongation, hepatotoxicity, neurotoxicity, cardiac function abnormalities. Participants who experienced other severe and life-threatening clinically-significant ATO-related AEs that are considered, in the judgement of the investigator, to increase participant risk with continued ATO treatment are also excluded.
Other inclusion/exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single-Dose PK Module: Sequence 1
Participants will receive IV ATO in a fasted state on Day 1, SY-2101 in a fed state on Day 8, and SY-210 in a fasted state on Day 15 during Weeks 6, 7, and 8 of any consolidation cycle being received as part of SOC treatment consolidation cycle.
|
SY-2101 will be administered per dose and schedule specified in arm description.
Other Names:
IV ATO will be administered per dose and schedule specified in arm description.
Other Names:
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Experimental: Single-Dose PK Module: Sequence 2
Participants will receive IV ATO in a fasted state on Day 1, SY-2101 in a fasted state on Day 8, and SY-2101 in a fed state on Day 15 during Weeks 6, 7, and 8 of any consolidation cycle being received as part of SOC treatment consolidation cycle.
|
SY-2101 will be administered per dose and schedule specified in arm description.
Other Names:
IV ATO will be administered per dose and schedule specified in arm description.
Other Names:
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Experimental: Single-Dose PK Comparability Module
Participants will receive two single-dose treatments of SY-2101, with separated from one another by approximately 1 week and separated from any preceding IV ATO dose by at least 72 hours.
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SY-2101 will be administered per dose and schedule specified in arm description.
Other Names:
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Experimental: Multiple-Dose IV Module
Participants will receive IV ATO, once daily (QD), 5 days/week for 28 days as a part of at least one cycle (Weeks 1 through 4) of SOC treatment consolidation.
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IV ATO will be administered per dose and schedule specified in arm description.
Other Names:
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Experimental: Multiple-Dose Oral Module
Participants will receive SY-2101, QD, 5 days/week for 28 days as a part of one cycle (Cycle 4; Weeks 1 through 4) of SOC treatment consolidation.
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SY-2101 will be administered per dose and schedule specified in arm description.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Single-Dose Module: Maximum Observed Plasma Concentration (Cmax) of SY-2101
Time Frame: Predose and up to 168 hours postdose
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Predose and up to 168 hours postdose
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Single-Dose Module: Area Under the Curve (AUC) of SY-2101
Time Frame: Predose and up to 168 hours postdose
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Predose and up to 168 hours postdose
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Multiple-Dose Module: Cmax of SY-2101
Time Frame: Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Multiple-Dose Module: AUC of SY-2101
Time Frame: Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Single-Dose Module: Cmax of ATO
Time Frame: Predose and up to 168 hours postdose
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Predose and up to 168 hours postdose
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Single-Dose Module: AUC of ATO
Time Frame: Predose and up to 168 hours postdose
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Predose and up to 168 hours postdose
|
Multiple-Dose Module: Cmax of ATO
Time Frame: Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
|
Multiple-Dose Module: AUC of ATO
Time Frame: Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
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Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
|
Number of Participants With Adverse Events
Time Frame: up to Day 23 for single-dose module and up to Day 56 for multiple-dose module
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up to Day 23 for single-dose module and up to Day 56 for multiple-dose module
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Medical Director, MD, Syros Pharmaceuticals Inc.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SY-2101-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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