A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia
Phase 1
Suspended
- Conditions
- Interventions
- Registration Number
- NCT04996030
- Lead Sponsor
- Syros Pharmaceuticals
- Brief Summary
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 ...
- Detailed Description
This study includes 4 parts. In the first part, enrolled participants will receive a single dose of IV ATO, followed a week later by a single dose of SY-2101, SY-2101 will be administered to participants in either a fed or a fasted condition. A week after that, participants will receive a second, a single dose of SY-2101, with some participants taking this d...
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 16
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
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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.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Multiple-Dose IV Module Arsenic Trioxide 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. Single-Dose PK Module: Sequence 2 SY-2101 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. Single-Dose PK Module: Sequence 2 Arsenic Trioxide 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. Single-Dose PK Module: Sequence 1 SY-2101 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. Multiple-Dose Oral Module SY-2101 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. Single-Dose PK Comparability Module SY-2101 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. Single-Dose PK Module: Sequence 1 Arsenic Trioxide 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.
- Primary Outcome Measures
Name Time Method Single-Dose Module: Maximum Observed Plasma Concentration (Cmax) of SY-2101 Predose and up to 168 hours postdose Single-Dose Module: Area Under the Curve (AUC) of SY-2101 Predose and up to 168 hours postdose Multiple-Dose Module: Cmax of SY-2101 Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26 Multiple-Dose Module: AUC of SY-2101 Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
- Secondary Outcome Measures
Name Time Method Single-Dose Module: AUC of ATO Predose and up to 168 hours postdose Number of Participants With Adverse Events up to Day 23 for single-dose module and up to Day 56 for multiple-dose module Single-Dose Module: Cmax of ATO Predose and up to 168 hours postdose Multiple-Dose Module: AUC of ATO Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26 Multiple-Dose Module: Cmax of ATO Predose and up to 6 hours postdose on Day 5 and up to 4 hours postdose on Day 26
Trial Locations
- Locations (8)
Weill Cornell Medical College
🇺🇸New York, New York, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States