- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04245397
Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome
A Phase 1, Open-Label, Dose-Escalation With Expansion Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Aaron D Schuler, PhD
- Phone Number: 21 253-833-8009
- Email: aschuler@syntrixbio.com
Study Locations
-
-
Florida
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Jacksonville, Florida, United States, 32224
- Recruiting
- Mayo Clinic
-
Contact:
- Amber Gessner
- Phone Number: 904-953-3739
- Email: Gessner.Amber@mayo.edu
-
Contact:
- Kaila Lopez
- Phone Number: 904-953-7746
- Email: Lopez.Kaila@mayo.edu
-
Principal Investigator:
- Hemant S Murthy, MD
-
Miami, Florida, United States, 33136
- Recruiting
- University of Miami
-
Contact:
- Namrata S Chandhok, MD
- Phone Number: 305-243-8238
- Email: namrata.chandhok@miami.edu
-
Principal Investigator:
- Namrata S Chandhok, MD
-
Orlando, Florida, United States, 32804
- Recruiting
- AdventHealth Medical Group & Bone Marrow Transplant at Orlando
-
Principal Investigator:
- Arlene Gayle, M.D.
-
Contact:
- Kristen Wing, RN,BSN,CCRP
- Phone Number: 407-303-8251
- Email: Kristen.Wing@adventhealth.com
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Tampa, Florida, United States, 33612
- Recruiting
- Moffitt Cancer Center
-
Contact:
- Caroline Wagstaff
- Phone Number: 813-745-5197
- Email: Caroline.Wagstaff@moffitt.org
-
Principal Investigator:
- David A Sallman, MD
-
Contact:
- Cyril Patra, MPH
- Phone Number: 813-745-2802
- Email: Cyril.Patra@moffitt.org
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-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University
-
Principal Investigator:
- Anthony M Hunter, MD
-
Contact:
- Shannon Gleason, MLS, CCRC
- Phone Number: 10808 404-778-4334
- Email: shannon.gleason@emory.edu
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Recruiting
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
Contact:
- Lisa A. Kelemen, RN, MSN
- Phone Number: 410-614-4618
- Email: lkeleme1@jhmi.edu
-
Principal Investigator:
- Amy E DeZern, MD, MHS
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Diagnosis of MDS by World Health Organization criteria, and either
International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk patients without 5q deletion:
i. Dose escalation portion: failed prior treatment with at least 4 cycles started of a hypomethylating agent (HMA; azacitidine or decitabine) defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy.
ii. Dose expansion portion: failed prior treatment defined as no response to treatment with at least 4 cycles started of HMA, loss of response at any time point, or progressive disease/intolerance to therapy ("HMA failure"); or no prior treatment with HMA ("HMA naive").
IPSS low risk or intermediate-1 risk patients with 5q deletion:
i. Dose escalation portion: failed prior treatment with at least 4 cycles started of lenalidomide and 4 cycles of hypomethylating agent (azacitidine or decitabine) defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy.
ii. Dose expansion portion: same as non-del(5q) lower risk cohort + requirement of failed prior treatment with lenalidomide defined as no response to treatment with at least 4 cycles started of lenalidomide, loss of response at any time point, or progressive disease/intolerance to therapy.
- IPSS intermediate-2 risk or high risk patients: HMA failure or HMA naïve as defined above.
- 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.
Exclusion Criteria:
- 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 with the exception of drugs that are considered absolutely essential for the care of the subject;
- 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 2 years except for local cancers that have been cured; or patients who have been adequately treated and have low risk of reoccurrence.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Escalation of SX-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.
|
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)
|
Experimental: Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in lower risk patients who have never received hypomethylating agents.
|
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)
|
Experimental: Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in lower risk patients who failed on hypomethylating agents.
|
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)
|
Experimental: Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) with decitabine in lower risk patients who have never received hypomethylating agents.
|
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.
Other Names:
|
Experimental: Expansion of SX-682 with decitabine (lower risk patients, failed on hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) with decitabine in lower risk patients who failed on hypomethylating agents.
|
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.
Other Names:
|
Experimental: Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in higher risk patients who failed on hypomethylating agents.
|
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)
|
Experimental: Expansion of SX-682 with decitabine (higher risk patients, naive to hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) with decitabine in higher risk patients who have never received hypomethylating agents.
|
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.
Other Names:
|
Experimental: Expansion of SX-682 with decitabine (higher risk patients, failed on hypomethylating agents)
Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) with decitabine in higher risk patients who failed on hypomethylating agents.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Up to 28 days in the 28 day Cycle 1.
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SX-682 Dose Limiting Toxicities (DLT)
Time Frame: Up to 28 days in the 28 day Cycle 1.
|
Number of participants experiencing DLTs.
|
Up to 28 days in the 28 day Cycle 1.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
At the end of Cycle 6 (each cycle is 28 days).
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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.
|
From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days).
|
Adverse Events
Time Frame: At the end of Cycle 6 (each cycle is 28 days).
|
Number of participants experiencing adverse events (AEs).
|
At the end of Cycle 6 (each cycle is 28 days).
|
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.
|
Day 1 of Cycle 1 (each cycle is 28 days).
|
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.
|
Day 15 of Cycle 1 (each cycle is 28 days).
|
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.
|
Day 15 of Cycle 1 (each cycle is 28 days).
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David A Sallman, MD, Moffitt Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SX682-MDS-102
- R44HL142389-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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