Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome
Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Immunotherapy, Chemokine receptor blockade, Myeloid-derived supressor cells
Eligibility Criteria
Inclusion Criteria:
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.
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;
- 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.
Sites / Locations
- Mayo ClinicRecruiting
- University of MiamiRecruiting
- AdventHealth Medical Group & Bone Marrow Transplant at OrlandoRecruiting
- Moffitt Cancer CenterRecruiting
- Emory UniversityRecruiting
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Dose Escalation of SX-682
Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents)
Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents)
Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)
Expansion of SX-682 with decitabine (lower risk patients, failed on hypomethylating agents)
Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents)
Expansion of SX-682 with decitabine (higher risk patients, naive to hypomethylating agents)
Expansion of SX-682 with decitabine (higher risk patients, failed on hypomethylating agents)
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.
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.
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.
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.
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.
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.
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.
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.