Treatment of Myelodysplastic Syndrome with SX-682 and Decitabine

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

This study is testing a new treatment combining SX-682 and decitabine to see if it helps people with Myelodysplastic Syndromes feel better and improve their health.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 151 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Syntrix Biosystems, Inc. (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 7 sites (Jacksonville, Florida and 6 other locations)
• Trial ID: NCT04245397 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of SX-682, an immunotherapy agent, both alone and in combination with decitabine, for patients with Myelodysplastic Syndromes (MDS). Participants will receive SX-682 orally twice daily over six 28-day cycles, with dose adjustments based on tolerability and response. The study aims to establish the maximum tolerated dose and recommended phase 2 dose, enrolling additional participants based on their treatment history and risk classification. The trial will also assess the impact of SX-682 on myeloid-derived suppressor cells and overall patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults diagnosed with Myelodysplastic Syndromes who have either failed prior treatments or are treatment-naive.

Not a fit: Patients with advanced MDS who have already received multiple lines of therapy or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with Myelodysplastic Syndromes, potentially improving their outcomes and quality of life.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches in treating hematological malignancies, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of MDS by World Health Organization criteria, and either

  1. 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").
  2. 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.
  3. 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:

  1. Renal glomerular filtration rate (GFR) ≥ 30 ml/min;
  2. Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 3.0 times upper limit of normal;
  3. Bilirubin \< 1.5 times upper limit of normal;
  4. No history of HIV being HIV positive;
  5. 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:

  1. QT interval \> 480 msec corrected using Fridericia's formula;
  2. Risk factors for Torsade de Pointes;
  3. Use of medication that prolongs the QT interval with the exception of drugs that are considered absolutely essential for the care of the subject;
  4. Myocardial infarction ≤ 6 months prior to first day of study drug treatment;
  5. 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.

Where this trial is running

Jacksonville, Florida and 6 other locations

• Mayo Clinic — Jacksonville, Florida, United States (Recruiting)
• University of Miami — Miami, Florida, United States (Recruiting)
• AdventHealth Medical Group & Bone Marrow Transplant at Orlando — Orlando, Florida, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• Emory University — Atlanta, Georgia, United States (Recruiting)
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
• Montefiore Medical Center — The Bronx, New York, United States (Recruiting)

Study contacts

• Principal investigator: David A Sallman, MD — Moffitt Cancer Center
• Study coordinator: Aaron D Schuler, PhD

Conditions Myelodysplastic Syndromes; Immunotherapy; Chemokine receptor blockade; Myeloid-derived supressor cells