Clinical Trials /

SX-682 Treatment in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy

NCT04245397

Description:

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).

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SX-682 Treatment in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy
  • 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

Clinical Trial IDs

  • ORG STUDY ID: SX682-MDS-102
  • SECONDARY ID: R44HL142389-01
  • NCT ID: NCT04245397

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
SX-682Oral Dose of S-682

Purpose

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).

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Oral Dose of S-682ExperimentalEscalating 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

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
                  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).

               2. 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.

               3. 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:

               1. Renal glomerular filtration rate (GFR) ≥ 60 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;

               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 3 years except for local cancers that have been
             cured.

          -  Within 14 days of the first study drug treatment requiring systemic treatment with
             either corticosteroids or immunosuppressive medications. Corticosteroid adrenal
             replacement doses are permitted.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:SX-682 Maximum Tolerated Dose (MTD)
Time Frame:Up to 21 days in the 21 day Cycle 1.
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Participants Experiencing a Treatment Response
Time Frame:At the end of Cycle 6 (each cycle is 21 days).
Safety Issue:
Description:The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.
Measure:SX-682 Delayed Dose Limiting Toxicities
Time Frame:From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 21 days).
Safety Issue:
Description:Number of delayed DLTs experienced by participants.
Measure:Adverse Events
Time Frame:At the end of Cycle 6 (each cycle is 21 days).
Safety Issue:
Description:Number of participants experiencing adverse events (AEs).
Measure:SX-682 Single Dose Maximum Plasma Concentration (Cmax)
Time Frame:Day 1 of Cycle 1 (each cycle is 21 days).
Safety Issue:
Description:Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.
Measure:SX-682 Steady-State Maximum Plasma Concentration (Css max)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days).
Safety Issue:
Description:Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
Measure:SX-682 Steady-State Minimum Plasma Concentration (Css min)
Time Frame:Day 15 of Cycle 1 (each cycle is 21 days).
Safety Issue:
Description:Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Syntrix Biosystems, Inc.

Trial Keywords

  • Immunotherapy
  • Chemokine receptor blockade
  • Myeloid-derived supressor cells

Last Updated

January 27, 2020