Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome

NCT04245397 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: SX682-MDS-102R44HL142389R44CA291622
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 7

Brief Summary

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).

Conditions

Myelodysplastic Syndromes

Keywords

Immunotherapy; Chemokine receptor blockade; Myeloid-derived supressor cells

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 28 days in the 28 day Cycle 1.

• SX-682 Dose Limiting Toxicities (DLT)

  Number of participants experiencing DLTs.

  Up to 28 days in the 28 day Cycle 1.

Secondary Outcomes (6)

• Participants Experiencing a Treatment Response

  At the end of Cycle 6 (each cycle is 28 days).

• SX-682 Delayed Dose Limiting Toxicities

  From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days).

• Adverse Events

  At the end of Cycle 6 (each cycle is 28 days).

• SX-682 Single Dose Maximum Plasma Concentration (Cmax)

  Day 1 of Cycle 1 (each cycle is 28 days).

• SX-682 Steady-State Maximum Plasma Concentration (Css max)

  Day 15 of Cycle 1 (each cycle is 28 days).

Study Arms (8)

Dose Escalation of SX-682

EXPERIMENTAL

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

Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents)

EXPERIMENTAL

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.

Drug: SX-682

Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents)

EXPERIMENTAL

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.

Drug: SX-682

Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)

EXPERIMENTAL

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in lower risk patients who have never received hypomethylating agents.

Drug: SX-682; Drug: Decitabine

Expansion of SX-682 with decitabine (lower risk patients, failed on hypomethylating agents)

EXPERIMENTAL

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in lower risk patients who failed on hypomethylating agents.

Drug: SX-682; Drug: Decitabine

Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents)

EXPERIMENTAL

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.

Drug: SX-682

Expansion of SX-682 with decitabine (higher risk patients, naive to hypomethylating agents)

EXPERIMENTAL

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in higher risk patients who have never received hypomethylating agents.

Drug: SX-682; Drug: Decitabine

Expansion of SX-682 with decitabine (higher risk patients, failed on hypomethylating agents)

EXPERIMENTAL

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in higher risk patients who failed on hypomethylating agents.

Drug: SX-682; Drug: Decitabine

Interventions

SX-682 DRUG

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)

Dose Escalation of SX-682; Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents); Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents); Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents); Expansion of SX-682 with decitabine (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 (lower risk patients, failed on hypomethylating agents); Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)

Decitabine DRUG

Decitabine is a hypomethylating agent.

Also known as: DEC-C

Expansion of SX-682 with decitabine (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 (lower risk patients, failed on hypomethylating agents); Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Emory University: collaborator
• University of Miami: collaborator
• Mayo Clinic: collaborator
• Montefiore Medical Center: collaborator
• National Cancer Institute (NCI): collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: collaborator
• Syntrix Biosystems, Inc.: lead
• AdventHealth: collaborator

Study Sites (7)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

AdventHealth Medical Group & Bone Marrow Transplant at Orlando

Orlando, Florida, 32804, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• David A Sallman, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aaron D Schuler, PhD

CONTACT

253-833-8009; aschuler@syntrixbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 28, 2020
• Study Start: June 30, 2020
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)