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

Primary Purpose

Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SX-682
Decitabine
Sponsored by
Syntrix Biosystems, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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) ≥ 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;
    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.
  • 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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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)

Arm Description

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.

Outcomes

Primary Outcome Measures

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
SX-682 Dose Limiting Toxicities (DLT)
Number of participants experiencing DLTs.

Secondary Outcome Measures

Participants Experiencing a Treatment Response
The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.
SX-682 Delayed Dose Limiting Toxicities
Number of delayed DLTs experienced by participants.
Adverse Events
Number of participants experiencing adverse events (AEs).
SX-682 Single Dose Maximum Plasma Concentration (Cmax)
Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.
SX-682 Steady-State Maximum Plasma Concentration (Css max)
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
SX-682 Steady-State Minimum Plasma Concentration (Css min)
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.

Full Information

First Posted
January 22, 2020
Last Updated
October 10, 2023
Sponsor
Syntrix Biosystems, Inc.
Collaborators
H. Lee Moffitt Cancer Center and Research Institute, National Heart, Lung, and Blood Institute (NHLBI), Johns Hopkins University, AdventHealth, Emory University, University of Miami, Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT04245397
Brief Title
Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 12, 2020 (Actual)
Primary Completion Date
March 2028 (Anticipated)
Study Completion Date
March 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syntrix Biosystems, Inc.
Collaborators
H. Lee Moffitt Cancer Center and Research Institute, National Heart, Lung, and Blood Institute (NHLBI), Johns Hopkins University, AdventHealth, Emory University, University of Miami, Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
Immunotherapy, Chemokine receptor blockade, Myeloid-derived supressor cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
151 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation of SX-682
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 with decitabine (lower risk patients, failed on hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 with decitabine (higher risk patients, naive to hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion of SX-682 with decitabine (higher risk patients, failed on hypomethylating agents)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
SX-682
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
DEC-C
Intervention Description
Decitabine is a hypomethylating agent.
Primary Outcome Measure Information:
Title
SX-682 Maximum Tolerated Dose (MTD)
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
Time Frame
Up to 28 days in the 28 day Cycle 1.
Title
SX-682 Dose Limiting Toxicities (DLT)
Description
Number of participants experiencing DLTs.
Time Frame
Up to 28 days in the 28 day Cycle 1.
Secondary Outcome Measure Information:
Title
Participants Experiencing a Treatment Response
Description
The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.
Time Frame
At the end of Cycle 6 (each cycle is 28 days).
Title
SX-682 Delayed Dose Limiting Toxicities
Description
Number of delayed DLTs experienced by participants.
Time Frame
From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days).
Title
Adverse Events
Description
Number of participants experiencing adverse events (AEs).
Time Frame
At the end of Cycle 6 (each cycle is 28 days).
Title
SX-682 Single Dose Maximum Plasma Concentration (Cmax)
Description
Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.
Time Frame
Day 1 of Cycle 1 (each cycle is 28 days).
Title
SX-682 Steady-State Maximum Plasma Concentration (Css max)
Description
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
Time Frame
Day 15 of Cycle 1 (each cycle is 28 days).
Title
SX-682 Steady-State Minimum Plasma Concentration (Css min)
Description
Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.
Time Frame
Day 15 of Cycle 1 (each cycle is 28 days).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aaron D Schuler, PhD
Phone
253-833-8009
Ext
21
Email
aschuler@syntrixbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Sallman, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amber Gessner
Phone
904-953-3739
Email
Gessner.Amber@mayo.edu
First Name & Middle Initial & Last Name & Degree
Kaila Lopez
Phone
904-953-7746
Email
Lopez.Kaila@mayo.edu
First Name & Middle Initial & Last Name & Degree
Hemant S Murthy, MD
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Namrata S Chandhok, MD
Phone
305-243-8238
Email
namrata.chandhok@miami.edu
First Name & Middle Initial & Last Name & Degree
Namrata S Chandhok, MD
Facility Name
AdventHealth Medical Group & Bone Marrow Transplant at Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristen Wing, RN,BSN,CCRP
Phone
407-303-8251
Email
Kristen.Wing@adventhealth.com
First Name & Middle Initial & Last Name & Degree
Arlene Gayle, M.D.
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cyril Patra, MPH
Phone
813-745-2802
Email
Cyril.Patra@moffitt.org
First Name & Middle Initial & Last Name & Degree
Caroline Wagstaff
Phone
813-745-5197
Email
Caroline.Wagstaff@moffitt.org
First Name & Middle Initial & Last Name & Degree
David A Sallman, MD
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shannon Gleason, MLS, CCRC
Phone
404-778-4334
Ext
10808
Email
shannon.gleason@emory.edu
First Name & Middle Initial & Last Name & Degree
Anthony M Hunter, MD
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa A. Kelemen, RN, MSN
Phone
410-614-4618
Email
lkeleme1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Amy E DeZern, MD, MHS

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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