This study will determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended Phase 2 dose (RP2D) of SX-682 in the treatment of patients with Myelodysplastic Syndromes (MDS).
Participants will receive twice daily oral SX-682 for six 28 day cycles. If patients are responding well to the treatment they can continue SX-682 treatment. The first participants will be administered 25 mg orally twice daily. Unless dose limiting toxicities occur, participants will enroll and receive the following increasing twice daily doses of SX-682: 50 mg, 100 mg, 200 mg, and 400 mg. After establishing the maximum tolerated dose 140 additional participants will be enrolled at the recommended phase 2 dose. Participants will receive continuous SX-682 twice daily oral therapy in 28-day cycles for a total of 6 cycles. The expansion dose cohort will be stratified into IPSS (a) low and intermediate-1 (N=20 SX-682 alone in HMA naive, N=20 SX-682 alone in HMA failure, N=20 SX-682 + DEC-C in HMA-naïve, N=20 SX-682 + DEC-C in HMA-failure) and (b) intermediate-2 and high risk (N=20 SX-682 alone in HMA failure, N=20 SX-682 + DEC-C in HMA-naive, N=20 SX-682 + DEC-C in HMA-failure) MDS. For patients responding well at the end of 6 cycles treatment may continue until disease progression or an adverse event leads to SX-682 discontinuation. Except for blood product transfusions, concurrent therapy for Myelodysplastic Syndromes is not permitted.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
151
SX-682 is an oral small molecule selective inhibitor of C-X-C Motif Chemokine Receptor 1 (CXCR1) and CX-C Motif Chemokine Receptor 2 (CXCR2)
Decitabine is a hypomethylating agent.
Mayo Clinic
Jacksonville, Florida, United States
RECRUITINGUniversity of Miami
Miami, Florida, United States
RECRUITINGAdventHealth Medical Group & Bone Marrow Transplant at Orlando
Orlando, Florida, United States
SX-682 Maximum Tolerated Dose (MTD)
Participants cohorts will be enrolled at increasing doses of SX-682. The highest SX-682 dose tested at which no more than 1 of 6 participants experiences a dose limiting toxicity will define the SX-682 MTD
Time frame: Up to 28 days in the 28 day Cycle 1.
SX-682 Dose Limiting Toxicities (DLT)
Number of participants experiencing DLTs.
Time frame: Up to 28 days in the 28 day Cycle 1.
Participants Experiencing a Treatment Response
The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.
Time frame: At the end of Cycle 6 (each cycle is 28 days).
SX-682 Delayed Dose Limiting Toxicities
Number of delayed DLTs experienced by participants.
Time frame: From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days).
Adverse Events
Number of participants experiencing adverse events (AEs).
Time frame: At the end of Cycle 6 (each cycle is 28 days).
SX-682 Single Dose Maximum Plasma Concentration (Cmax)
Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.
Time frame: Day 1 of Cycle 1 (each cycle is 28 days).
SX-682 Steady-State Maximum Plasma Concentration (Css max)
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
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Moffitt Cancer Center
Tampa, Florida, United States
RECRUITINGEmory University
Atlanta, Georgia, United States
RECRUITINGSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
RECRUITINGMontefiore Medical Center
The Bronx, New York, United States
RECRUITINGTime frame: Day 15 of Cycle 1 (each cycle is 28 days).
SX-682 Steady-State Minimum Plasma Concentration (Css min)
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
Time frame: Day 15 of Cycle 1 (each cycle is 28 days).