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 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.
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 dose in a fed state and other participants taking this dose in a fasted condition. After
each of these doses, blood draws and safety assessments will be performed. In the second
part, enrolled participants will receive IV ATO according to the standard of care, with
collection of blood and safety assessments. In the third part, 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. In the fourth part, enrolled participants will receive two single-dose treatments
of SY-2101 approximately one week apart.
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 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.
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
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.
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, Inc.
Verification Date
February 2023