A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia

NCT04996030 | Suspended Phase 1 FDA Drug

• 1 other identifier: SY-2101-101
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

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 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.

Conditions

Acute Promyelocytic Leukemia

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Single-Dose Module: Cmax of ATO

  Predose and up to 168 hours postdose

• Single-Dose Module: AUC of ATO

  Predose and up to 168 hours postdose

• 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

• 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

• Number of Participants With Adverse Events

  up to Day 23 for single-dose module and up to Day 56 for multiple-dose module

Study Arms (5)

Single-Dose PK Module: Sequence 1

EXPERIMENTAL

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.

Drug: SY-2101; Drug: Arsenic Trioxide

Single-Dose PK Module: Sequence 2

EXPERIMENTAL

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.

Drug: SY-2101; Drug: Arsenic Trioxide

Single-Dose PK Comparability Module

EXPERIMENTAL

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.

Drug: SY-2101

Multiple-Dose IV Module

EXPERIMENTAL

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.

Drug: Arsenic Trioxide

Multiple-Dose Oral Module

EXPERIMENTAL

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.

Drug: SY-2101

Interventions

SY-2101 DRUG

SY-2101 will be administered per dose and schedule specified in arm description.

Also known as: Oral ATO, Oral Arsenic Trioxide

Multiple-Dose Oral Module; Single-Dose PK Comparability Module; Single-Dose PK Module: Sequence 1; Single-Dose PK Module: Sequence 2

Arsenic Trioxide DRUG

IV ATO will be administered per dose and schedule specified in arm description.

Also known as: IV ATO, Trisenox®, IV Arsenic Trioxide

Multiple-Dose IV Module; Single-Dose PK Module: Sequence 1; Single-Dose PK Module: Sequence 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Syros Pharmaceuticals: lead

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60208, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ravandi F, Rangaraju S, Kantarjian H, Garcia-Manero G, Yilmaz M, Baker K, Hall T, Grabenstein J, Roy P, Zamboni BA, Zamboni WC, Warlick E, Kelly M, Roth DA, Ghiaur G. A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia. Blood Adv. 2025 May 13;9(9):2136-2143. doi: 10.1182/bloodadvances.2024015453.

  PMID: 40020161 DERIVED

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Arsenic Trioxide; cyclo-tetrakis(bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato)mu-oxotitanium(IV))

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Medical Director, MD

  Syros Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The characterization of single-dose PK will be conducted in an open-label, randomized crossover 3-period, 3-treatment, 2-sequence design, separated by ≥1 week of washout.

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 9, 2021
• Study Start: September 17, 2021
• Primary Completion: January 3, 2024
• Study Completion: April 1, 2024
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)