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

Sponsor

Syntrix Biosystems, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04245397

Collaborator

H. Lee Moffitt Cancer Center and Research Institute (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Johns Hopkins University (Other), AdventHealth (Other)

Enrollment

Locations

Arm

45.6

Anticipated Duration (Months)

21.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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).

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.

Study Design

Study Type:

Interventional

Anticipated 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.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

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

SX-682 Maximum Tolerated Dose (MTD) [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
SX-682 Dose Limiting Toxicities (DLT) [Up to 28 days in the 28 day Cycle 1.]
Number of participants experiencing DLTs.

Secondary Outcome Measures

Participants Experiencing a Treatment Response [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.
SX-682 Delayed Dose Limiting Toxicities [From the beginning of Cycle 2 to the end of Cycle 6 (each cycle is 28 days).]
Number of delayed DLTs experienced by participants.
Adverse Events [At the end of Cycle 6 (each cycle is 28 days).]
Number of participants experiencing adverse events (AEs).
SX-682 Single Dose Maximum Plasma Concentration (Cmax) [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.
SX-682 Steady-State Maximum Plasma Concentration (Css max) [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.
SX-682 Steady-State Minimum Plasma Concentration (Css min) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AdventHealth Medical Group & Bone Marrow Transplant at Orlando	Orlando	Florida	United States	32804
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287