Phase 2
Completed N=124
Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
Source: ClinicalTrials.gov NCT02103478 ↗Enrolled (actual)
124
Serious AEs
74.2%
Results posted
Oct 2020
Primary outcomePrimary: Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 — 53.6; 68.9; 94.8; 221 ng*h/mL
Summary
This first-in-human, 3-stage, open-label study evaluated the safety and pharmacokinetics of ASTX727, as well as determined the dose for later stages.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 |
53.6; 68.9; 94.8; 221; 146 | — |
| PRIMARY Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2 |
93.52; 97.59 | — |
| PRIMARY Number of Participants With Dose-limiting Toxicity in Phase 1 |
0; 0; 0; 0; 1 | — |
| PRIMARY Mean Maximum %LINE Demethylation in Phase 2 |
11.159; 10.077; 11.303; 12.665; 9.833; 8.134 | — |
| PRIMARY Number of Participants With Overall Response in Phase 2 |
29; 19 | — |
| SECONDARY Area Under the Concentration Versus Time Curve of Cedazuridine (E7727) and Cedazuridine-epimer |
1650; 1990; 3190; 4830; 3490; 2370 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Cedazuridine (E7727) and Cedazuridine-epimer |
309; 376; 636; 697; 570; 451 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Cedazuridine (E7727) and Cedazuridine-epimer |
3; 3; 3; 3; 3; 3 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Decitabine |
54.0; 76.5; 80.9; 161; 138; 126 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Decitabine in Phase 2 |
1.00; 0.95 | — |
| SECONDARY Duration of Complete Response in Phase 1 |
546.00; 364.00; 470.00; 29.00; 399.0 | — |
| SECONDARY Duration of Complete Response in Phase 2 - Kaplan-Meier Estimate |
413.0; 155.0 | — |
| SECONDARY Mean Maximum %LINE Demethylation in Phase 1 |
-8.3; -9.2; -10.5; -12.1; -11.7; -8.0 | — |
| SECONDARY Number of Participants With Overall Response in Phase 1 |
4; 3; 2; 1; 3 | — |
| SECONDARY Number of Participants With Adverse Events |
6; 6; 6; 6; 19; 50 | — |
| SECONDARY Number of Participants With Hematological Improvement |
4; 3; 2; 0; 3; 8 | — |
| SECONDARY Number of Participants With Transfusion Independence |
2; 0; 3; 0; 2; 11 | — |
| SECONDARY Number of Participants to Reach Acute Myeloid Leukemia (AML) or Death |
4; 5; 6; 5; 11; 22 | — |
| SECONDARY Number of Participants With Overall Survival |
6; 5; 6; 5; 15; 26 | — |
Eligibility Criteria
Inclusion Criteria
- International Prognostic Scoring System (IPSS) low, intermediate -1, intermediate-2, or high risk MDS (including chronic myelomonocytic leukemia; CMML) in Dose Escalation and Dose Confirmation-Randomization; only intermediate-2, or high risk MDS in Dose Confirmation-Open Label
- Eastern Cooperative Oncology Group (ECOG) 0 to 2
- No major surgery within 2 weeks of starting study treatment
- No cytotoxic chemotherapy within 2 weeks of starting study treatment
- Able to swallow pills
Exclusion Criteria
- Previous treatment with 2 or more courses of decitabine (all stages) or azacitidine (Dose Confirmation stage only)
- Treatment with investigational therapy within 2 weeks of study treatment
- Uncontrolled medical disease(s) or active, uncontrolled infection
- Diagnosed with acute myeloid leukemia (AML)
- Active uncontrolled gastric or duodenal ulcer
- Known history of HIV or hepatitis C or B
Data sourced from ClinicalTrials.gov (NCT02103478). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.