Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome
Cancer-Related Syndrome
Leukemia
Myelodysplastic Syndromes (MDS)
18 Years and older, Male and Female
SX682-MDS-102 (primary)
NCI-2020-04523
R44HL142389-01
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).
Objectives
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.
Eligibility
- 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.
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