Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
Myelodysplastic Syndrome, MDS
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Myelodysplastic Syndrome, MDS
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
Sites / Locations
- Mayo Clinic
- University of Southern California
- University of Chicago
- Horizon Oncology
- Johns Hopkins
- Massachusetts General Hospital
- Dana Farber Cancer Institute
- John Theurer Cancer Center/ Hackensack University Medical Center
- Roswell Park Cancer Institute
- Weill Cornell Medical College - New York Presbyterian Hospital
- Vanderbilt Ingram Cancer Center
- M. D. Anderson
- Medical College of Wisconsin
- University of Alberta Hospital
- Sunnybrook Health Sciences Centre, Odette Cancer Centre
- Princess Margaret Cancer Center
- Hôpital Maisonneuve-Rosemont
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Phase 1 Dose Escalation
Phase 2 Dose Confirmation
Phase 2 Fixed-Dose Combination
Starting cohort was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (E7727) (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine (E7727)/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.