Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04245397
Recruitment Status : Recruiting
First Posted : January 28, 2020
Last Update Posted : September 23, 2021
Sponsor:
Collaborators:
H. Lee Moffitt Cancer Center and Research Institute
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Syntrix Biosystems, Inc.

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).

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: SX-682 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : May 12, 2020
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral Dose of S-682
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
Drug: SX-682 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)




Primary Outcome Measures :
  1. SX-682 Maximum Tolerated Dose (MTD) [ Time Frame: Up to 28 days in the 28 day Cycle 1. ]
    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

  2. SX-682 Dose Limiting Toxicities (DLT) [ Time Frame: Up to 28 days in the 28 day Cycle 1. ]
    Number of participants experiencing DLTs.


Secondary Outcome Measures :
  1. Participants Experiencing a Treatment Response [ Time Frame: At the end of Cycle 6 (each cycle is 28 days). ]
    The percentage of participants experiencing a complete remission, partial remission, or stable disease according to the International Working Group Response Criteria.

  2. SX-682 Delayed Dose Limiting Toxicities [ Time Frame: From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days). ]
    Number of delayed DLTs experienced by participants.

  3. Adverse Events [ Time Frame: At the end of Cycle 6 (each cycle is 28 days). ]
    Number of participants experiencing adverse events (AEs).

  4. SX-682 Single Dose Maximum Plasma Concentration (Cmax) [ Time Frame: Day 1 of Cycle 1 (each cycle is 28 days). ]
    Blood samples will be collected before and after the first dose of SX-682 on Day 1 of Cycle 1.

  5. SX-682 Steady-State Maximum Plasma Concentration (Css max) [ Time Frame: Day 15 of Cycle 1 (each cycle is 28 days). ]
    Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.

  6. SX-682 Steady-State Minimum Plasma Concentration (Css min) [ Time Frame: Day 15 of Cycle 1 (each cycle is 28 days). ]
    Blood samples will be collected before and after the first dose of SX-682 on Day 15 of Cycle 1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04245397


Contacts
Layout table for location contacts
Contact: Stuart J Kahn, MD 2065240214 skahn@syntrixbio.com

Locations
Layout table for location information
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Kimberly Clark    813-745-7362    Kimberly.Clark@moffitt.org   
Principal Investigator: David A Sallman, MD         
Sponsors and Collaborators
Syntrix Biosystems, Inc.
H. Lee Moffitt Cancer Center and Research Institute
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: David A Sallman, MD Moffitt Cancer Center
Layout table for additonal information
Responsible Party: Syntrix Biosystems, Inc.
ClinicalTrials.gov Identifier: NCT04245397    
Other Study ID Numbers: SX682-MDS-102
R44HL142389-01 ( U.S. NIH Grant/Contract )
First Posted: January 28, 2020    Key Record Dates
Last Update Posted: September 23, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Syntrix Biosystems, Inc.:
Immunotherapy
Chemokine receptor blockade
Myeloid-derived supressor cells
Additional relevant MeSH terms:
Layout table for MeSH terms
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease Progression
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease Attributes