The purpose of this study is to to determine the recommended dose level of JNJ-30979754 (decitabine) as well as to assess the safety and effectiveness in patients with Myelodysplastic Syndrome (MDS).
This is an open-label (both physician and patient know the name and dosage of drug), multi-center study. This study consists of two parts, Phase I and Phase II. In Phase I, approximately 9 participants will be enrolled ie, 3 participants for dose level 1 (15 mg/m2 of JNJ-30979754) and 6 participants for dose level 2 (20 mg/m2 of JNJ-30979754). Once the tolerability of 20 mg/m2 is confirmed additional 30 participants will be included to receive 20 mg/m2 and approximate total participants in Phase II will be 36. This study will include screening period (within 14 days prior to the day of initial administration of Cycle 1) and dosing period (1 cycle consists of administration of study medication for first 5 consecutive days + rested for 23 days; ie, total 28 days). Cycles will be reapeated in participants in whom decitabine was expected to be effective. Safety evaluations will include assessment of adverse events, vital signs, body weight, clinical laboratory tests: hematology, blood biochemistry and urinalysis, cardiopulmonary function tests: ECG, chest X ray and oximeter analysis.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
JNJ-30979754 (decitabine) 15 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1.
Phase I: JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1. Phase II: JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles until the decitabine was expected to be effective in participants.
Unnamed facility
Fukuoka, Japan
Unnamed facility
Hamamatsu, Japan
Unnamed facility
Hidaka, Japan
Unnamed facility
Nagasaki, Japan
Unnamed facility
Nagoya, Japan
Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000)
IWG response criteria (2000) - CR: bone marrow evaluations show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes.
Time frame: Up to 1 years after the last participant enrolled
Phase I and II: Number of Participants Who Experienced Adverse Events
Time frame: Up to 1.5 years after the last participant enrolled
Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax)
Time frame: Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1
Phase I: Area Under the Plasma Concentration-time Curve (AUC)
Area under the curve from time zero to extrapolated infinite time (AUC Infinity) and area under the curve from time zero to last quantifiable concentration (AUC Last).
Time frame: Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1
Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)
IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia; PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes; HI: hemoglobin \< 11 g/dL (erythroid); platelet \< 100,000/mL; neutrophils \< 1,000/mL.
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Unnamed facility
Shinjuku, Japan
Unnamed facility
Tokyo, Japan
Time frame: Up to 28 Days of treatment Cycle 1
Phase II: Median Time to Remission
Median time required for the participants to achieve remission (complete remission+partial remission).
Time frame: Up to 1.5 years after the last participant enrolled
Phase II: Median Time to Improvement
Median time required for the participants to achieve overall improvement (complete remission+partial remission+hematologic improvement)
Time frame: Up to 1.5 years after the last participant enrolled
Phase II: Median Duration of Remission
Median time duration for which participants achieved remission (complete remission+partial remission).
Time frame: Up to 1.5 years after the last participant enrolled
Phase II: Median Duration of Overall Improvement
Median time duration for which participants achieved overall improvement (complete remission+partial remission+hematologic improvement).
Time frame: Up to 1.5 years after the last participant enrolled
Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)
IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes. HI: hemoglobin \< 11 g/dL (erythroid); platelet \< 100,000/mL; neutrophils \< 1,000/mL.
Time frame: Up to 1.5 years after the last participant enrolled
Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial)
IWG 2000 - Major: disappearance of cytogenetic abnormality; Minor: 50% or more reduction in abnormal metaphases. IWG 2006 - Complete: disappearance of the chromosomal abnormality without appearance of new ones; Partial: At least 50% reduction of the chromosomal abnormality.
Time frame: Up to 1.5 years after the last participant enrolled