Leukemia
Conditions
Keywords
Acute myelogenous leukemia, myelodysplastic Syndrome, cancer
Brief summary
The purpose of this study is to determine the pharmacokinetics (PK) of decitabine administered to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
Interventions
Intravenous injection; total dose-per-cycle was 135 mg/m\^2 of decitabine.
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient had to meet the following criteria to be eligible for the study: 1. Patients with MDS (de novo or secondary) must have been 60 years or older and have had disease fitting any of the recognized French-American-British classifications OR chronic myelomonocytic leukemia (with white blood cell \[WBC\] \<12,000/μL) AND have had an International Prognostic Scoring System score of ≥1.5 as determined by complete blood count, bone marrow assessment and bone marrow cytogenetics within 30 days of study entry. 2. Patients with AML (≥30% bone marrow blasts) must have been age 18 years or older and had previously received standard induction chemotherapy and/or had failed approved therapies. 3. Must have had Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 4. Must have signed an Institutional Review Board (IRB)-approved informed consent form, indicating his/her awareness of the investigational nature of this study and its potential hazards prior to initiation of any study-specific procedures or treatment. 5. Must have had adequate renal and hepatic function (creatinine ≤2.0 mg/dL, total bilirubin \<2.0 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3.0 X institutional upper limit of normal). 6. Must have had life expectancy of at least 12 weeks. 7. Must have recovered from all toxic effects of all prior therapy before entry into this study.
Exclusion criteria
1. Patients with MDS must not have been candidates for high-dose chemotherapy, bone marrow or stem cell transplant. 2. Must not have had acute promyelocytic leukemia (M3 classification). 3. Must not have received immunosuppressive therapy for 30 days prior to study entry. 4. Must not have had central nervous system (CNS) leukemia. 5. Must not have received systemic corticosteroids, interferon, interleukins or other hormonal therapy within 30 days prior to study entry. Use of corticosteroids (topical and inhaled corticosteroids) was permitted and prophylactic steroids may have been used to treat or prevent transfusion reactions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Total Body Clearance (Calculated From Rate and Concentration) | Day 1, Day 2, Day 3 | 3-hour IV infusion, every 8 hours for three consecutive days. Average Total Body Clearance was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3). |
| Cmax (Maximum Plasma Concentration) | Day 1, Day 2, Day 3 | 3-hour IV infusion, every 8 hours for three consecutive days. Cmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3). |
| Tmax (Time at Which Cmax First Observed) | Day 1, Day 2, Day 3 | 3-hour IV infusion, every 8 hours for three consecutive days. Tmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3). |
| AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | Day 1, Day 2, day 3 | 3-hour IV infusion, every 8 hours for three consecutive days. AUC (0-∞) was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | 6 weeks | Summary of All Adverse Events (AEs) by Maximum Grade Occurring in \>= 10% Patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Decitabine A 15 mg/m\^2 dose was administered as a 3-hour IV infusion every 8 hours for 3 consecutive days in acute myelogenous leukemia/myelodysplastic syndrome patients. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Decitabine |
|---|---|
| Age Continuous | 68.2 years STANDARD_DEVIATION 11.12 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 9 / 16 |
Outcome results
Primary
AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity
3-hour IV infusion, every 8 hours for three consecutive days. AUC (0-∞) was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).
Time frame: Day 1, Day 2, day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Decitabine | AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | Day 1 | 163 ng∙hr/mL | Standard Deviation 101 |
| Decitabine | AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | Day 2 | 152 ng∙hr/mL | Standard Deviation 90.5 |
| Decitabine | AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity | Day 3 | 158 ng∙hr/mL | Standard Deviation 101 |
Primary
Average Total Body Clearance (Calculated From Rate and Concentration)
3-hour IV infusion, every 8 hours for three consecutive days. Average Total Body Clearance was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).
Time frame: Day 1, Day 2, Day 3
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Decitabine | Average Total Body Clearance (Calculated From Rate and Concentration) | 129 L/hr/m^2 | 48.6 |
Primary
Cmax (Maximum Plasma Concentration)
3-hour IV infusion, every 8 hours for three consecutive days. Cmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).
Time frame: Day 1, Day 2, Day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Decitabine | Cmax (Maximum Plasma Concentration) | Day 1 | 73.8 ng/mL | Standard Deviation 48.6 |
| Decitabine | Cmax (Maximum Plasma Concentration) | Day 2 | 64.8 ng/mL | Standard Deviation 40.2 |
| Decitabine | Cmax (Maximum Plasma Concentration) | Day 3 | 77.0 ng/mL | Standard Deviation 62.5 |
Primary
Tmax (Time at Which Cmax First Observed)
3-hour IV infusion, every 8 hours for three consecutive days. Tmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).
Time frame: Day 1, Day 2, Day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Decitabine | Tmax (Time at Which Cmax First Observed) | Day 1 | 2.49 hours | Standard Deviation 0.7 |
| Decitabine | Tmax (Time at Which Cmax First Observed) | Day 2 | 2.53 hours | Standard Deviation 0.69 |
| Decitabine | Tmax (Time at Which Cmax First Observed) | Day 3 | 2.29 hours | Standard Deviation 0.63 |
Secondary
Safety: The Most Frequently Reported Adverse Events (Regardless of Causality)
Summary of All Adverse Events (AEs) by Maximum Grade Occurring in \>= 10% Patients
Time frame: 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Blood & Lymphatic System Disorders | 4 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Cardiac Disorders | 2 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Eye Disorders | 2 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Gastrointestinal Disorders | 11 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | General Disorders & Administration Site Conditions | 14 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Infections and Infestations | 7 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Investigations - Weight decreased | 2 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Metabolism and Nutrition | 5 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Musculoskeletal and Connective Tissue Disorders | 6 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Nervous System Disorders | 8 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Psychiatric Disorders | 5 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Respiratory, Thoracic and Mediastinal Disorders | 13 Participants |
| Decitabine | Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) | Skin and Subcutaneous Tissue Disorders | 9 Participants |