SX-682 Treatment in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy
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|ClinicalTrials.gov Identifier: NCT04245397|
Recruitment Status : Recruiting
First Posted : January 28, 2020
Last Update Posted : February 9, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Drug: SX-682||Phase 1|
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 40 additional participants will be enrolled at the maximum tolerated dose (or at the highest dose studied if a maximum tolerated dose is not identified). Participants will receive continuous SX-682 twice daily oral therapy in 28-day cycles for a total of 6 cycles. 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 (Clinical Trial)|
|Estimated Enrollment :||64 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||In this sequential model initially participant groups will enroll to receive SX-682 for six 28 day cycles in a dose escalation phase. A 3 + 3 participant design will be used to determine the safe dose. After 6 cycles at the specified dose of SX-682, SX-682 treatment can be continued. Once the safe dose level of SX-682 is determined, then participants will be enrolled at the this safe dose level of SX-682 in an expansion phase.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-Label, Dose-Escalation With Expansion Study of SX-682 in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy|
|Actual Study Start Date :||May 12, 2020|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||March 2024|
Experimental: Oral Dose of S-682
Escalating oral doses of SX-682 (study drug) of 25, 50, 100, 200 and 400 mg twice-daily (i.e., 50, 100, 200, 400 and 800 mg total each day.
Drug: SX-682 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)
- SX-682 Maximum Tolerated Dose (MTD) [ Time Frame: Up to 28 days in the 28 day Cycle 1. ]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
- SX-682 Dose Limiting Toxicities (DLT) [ Time Frame: Up to 28 days in the 28 day Cycle 1. ]Number of participants experiencing DLTs.
- Participants Experiencing a Treatment Response [ Time Frame: At the end of Cycle 6 (each cycle is 28 days). ]The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.
- SX-682 Delayed Dose Limiting Toxicities [ Time Frame: From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days). ]Number of delayed DLTs experienced by participants.
- Adverse Events [ Time Frame: At the end of Cycle 6 (each cycle is 28 days). ]Number of participants experiencing adverse events (AEs).
- SX-682 Single Dose Maximum Plasma Concentration (Cmax) [ Time Frame: Day 1 of Cycle 1 (each cycle is 28 days). ]Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.
- SX-682 Steady-State Maximum Plasma Concentration (Css max) [ Time Frame: Day 15 of Cycle 1 (each cycle is 28 days). ]Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
- SX-682 Steady-State Minimum Plasma Concentration (Css min) [ Time Frame: Day 15 of Cycle 1 (each cycle is 28 days). ]Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Diagnosis of MDS by World Health Organization criteria, and either
International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk without 5q deletion and failed treatment (no response, loss of response, progressive disease/treatment intolerance) following:
i. 4 cycles hypomethylating agent; or ii. 4 cycles hypomethylating agent, or lenalidomide or erythropoietin stimulating agent (ESA).
IPSS low risk or intermediate-1 risk with 5q deletion and failed treatment following:
i. 4 cycles of lenalidomide and hypomethylating agent; or ii. 4 cycles of lenalidomide.
- IPSS intermediate-2 risk or high risk and failed treatment following 4 cycles hypomethylating agent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
Screening laboratory values:
- Renal glomerular filtration rate (GFR) ≥ 30 ml/min;
- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 3.0 times upper limit of normal;
- Bilirubin < 1.5 times upper limit of normal;
- No history of HIV being HIV positive;
- No active Hepatitis B or Hepatitis C infection.
- Life expectancy ≥ 12 weeks.
- Women of childbearing potential (WOCBP) must use study specified contraception.
- WOCBP demonstrate negative pregnancy test.
- Not breastfeeding.
- Men sexually active must use study specified contraception.
- Use of chemotherapeutic agents or experimental agents for MDS within 14 days of the first day of study drug treatment.
- Use of erythroid stimulating agents, Granulocyte-colony stimulating factor (G-CSF), or Granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days of the first day of study drug treatment, or during the study.
- Mean triplicate heart rate-corrected QT interval (QTc) > 500 msec.
Any of the following cardiac abnormalities:
- QT interval > 480 msec corrected using Fridericia's formula;
- Risk factors for Torsade de Pointes;
- Use of medication that prolongs the QT interval;
- Myocardial infarction ≤ 6 months prior to first day of study drug treatment;
- Unstable angina pectoris or serious uncontrolled cardiac arrhythmia.
- Any serious or uncontrolled medical disorder.
- Prior malignancy within the previous 3 years except for local cancers that have been cured.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Use of other investigational drugs within 30 days of study drug administration.
- Major surgery within 4 weeks of study drug administration.
- Live-virus vaccination within 30 days of study drug administration.
- Allergy to study drug component.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04245397
|Contact: Stuart J Kahn, MD||(253) email@example.com|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Namrata S Chandhok, MD 305-243-8238 firstname.lastname@example.org|
|Principal Investigator: Namrata S Chandhok, MD|
|AdventHealth Medical Group & Bone Marrow Transplant at Orlando||Recruiting|
|Orlando, Florida, United States, 32804|
|Contact: Kristen Wing, RN, BSN, BMTCN 407-303-8251 Kristen.Wing@adventhealth.com|
|Principal Investigator: Arlene Gayle, M.D.|
|Moffitt Cancer Center||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Julian Greenup, CRC 813-745-3079 Julian.Greenup@moffitt.org|
|Principal Investigator: David A Sallman, MD|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Contact: Shannon Gleason, MLS, CCRC 404-778-4334 ext 10808 email@example.com|
|Principal Investigator: Anthony M Hunter, MD|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Lisa A. Kelemen, RN, MSN 410-614-4618 firstname.lastname@example.org|
|Principal Investigator: Amy D DeZern, MD, MHS|
|Principal Investigator:||David A Sallman, MD||Moffitt Cancer Center|
|Responsible Party:||Syntrix Biosystems, Inc.|
|Other Study ID Numbers:||
R44HL142389-01 ( U.S. NIH Grant/Contract )
|First Posted:||January 28, 2020 Key Record Dates|
|Last Update Posted:||February 9, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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