Brief Title
A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia
Official Title
An Open-label Phase 1 Study to Evaluate Pharmacokinetics, Safety, and Tolerability of SY-2101 in Adult Patients With Acute Promyelocytic Leukemia
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 form of a drug called arsenic trioxide
(ATO). ATO is already used to treat APL in a form that is given as an intravenous (IV)
infusion (through a needle in the arm). SY-2101 is a different form of ATO that is taken
orally (by mouth).
This trial will include participants with low-risk APL in remission, who are receiving
standard of care treatment with all-trans-retinoic acid (ATRA) and intravenous ATO, during
the consolidation phase of chemotherapy with low-risk APL. The participants in this trial
will get continued treatment with ATO and ATRA to help keep their cancer from coming back.
There will be some weeks when participants receive intravenous ATO and others when they
receive SY-2101 (ATO taken orally).
Detailed Description
This study includes 3 parts: during one part, enrolled participants will receive a single
dose of IV ATO, and a week later a single dose of SY-2101 either in the fed or fasted
condition, and a week after that, a single dose of SY-2101 in the fed or fasted condition.
After each of these doses, blood draws and safety assessments will be performed. In another
part of the study, enrolled participants will receive IV ATO according to the standard of
care, with collection of blood and safety assessments. In the third part of the study,
enrolled participants who are documented to be in molecular remission will receive SY-2101 in
place of IV ATO during the 4th cycle of consolidation, with the collection of blood and
safety assessments throughout the cycle. Participants do not need to participate in all parts
of the study to enroll.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Single-Dose Module: Maximum Observed Plasma Concentration (Cmax) of SY-2101
Secondary Outcome
Single-Dose Module: Cmax of ATO
Condition
Acute Promyelocytic Leukemia
Intervention
SY-2101
Study Arms / Comparison Groups
Single-Dose PK Module: Sequence 1
Description: Participants will receive ATO as IV infusion in fasted state on Day 1, SY-2101 administered orally in fed state on Day 8, and SY-2101 administered orally in fasted state on Day 15 during Weeks 6, 7, and 8 of any consolidation cycle being received as part of SOC treatment consolidation cycle
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
24
Start Date
September 17, 2021
Completion Date
March 2023
Primary Completion Date
March 2023
Eligibility Criteria
Inclusion Criteria:
- Participants must have a diagnosis of low risk 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 must have received ATO plus ATRA induction therapy and must have received
or are 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.
- 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/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).
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director, MD, (617) 744-1340, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04996030
Organization ID
SY-2101-101
Responsible Party
Sponsor
Study Sponsor
Syros Pharmaceuticals
Study Sponsor
Medical Director, MD, Study Director, Syros Pharmaceuticals
Verification Date
September 2021