A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT00796003
First received: November 20, 2008
Last updated: October 10, 2013
Last verified: October 2013
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: JNJ-30979754 15 mg/m2
Drug: JNJ-30979754 20 mg/m2
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • 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) [ Time Frame: Up to 1 years after the last participant enrolled ] [ Designated as safety issue: No ]
    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.

  • Phase I and II: Number of Participants Who Experienced Adverse Events [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Phase I: Area Under the Plasma Concentration-time Curve (AUC) [ 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 ] [ Designated as safety issue: No ]
    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).

  • 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) [ Time Frame: Up to 28 Days of treatment Cycle 1 ] [ Designated as safety issue: No ]
    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.

  • Phase II: Median Time to Remission [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    Median time required for the participants to achieve remission (complete remission+partial remission).

  • Phase II: Median Time to Improvement [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    Median time required for the participants to achieve overall improvement (complete remission+partial remission+hematologic improvement)

  • Phase II: Median Duration of Remission [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    Median time duration for which participants achieved remission (complete remission+partial remission).

  • Phase II: Median Duration of Overall Improvement [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    Median time duration for which participants achieved overall improvement (complete remission+partial remission+hematologic improvement).

  • 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) [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    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.

  • Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial) [ Time Frame: Up to 1.5 years after the last participant enrolled ] [ Designated as safety issue: No ]
    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.


Enrollment: 39
Study Start Date: July 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: JNJ-30979754 15 mg/m2
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
Drug: JNJ-30979754 15 mg/m2
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.
Other Name: decitabine
Experimental: Phase I: JNJ-30979754 20 mg/m2
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
Drug: JNJ-30979754 20 mg/m2
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.
Other Name: decitabine
Experimental: Phase II: JNJ-30979754 20 mg/m2
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
Drug: JNJ-30979754 20 mg/m2
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.
Other Name: decitabine

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Myelodysplastic syndrome (de novo or secondary) fitting any of the recognized French-American-British classifications: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia with white blood cells less than 13,000 /mm3
  • International Prognostic Scoring System (IPSS) greater than or equal to 0.5 (Intermediate-1, Intermediate-2 or high risk) by bone marrow assessment and bone marrow cytogenetics within 28 days before study registration
  • 20 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Normal renal and hepatic function

Exclusion Criteria:

  • Acute Myeloid Leukemia (AML) with bone marrow blasts greater than or equal to 30%
  • Participants with a history of high-dose cytarabine (Ara-C) therapy (greater than 1,000 mg/m2/day)
  • Participants administered adrenal cortex hormones or anabolic hormones within 7 days of study initiation
  • Participants who have received a colony stimulating factor (CSF) formulation within 7 days of study initiation
  • Active double cancer
  • Uncontrolled cardiac disease or cognitive heart failure
  • Uncontrolled restrictive or obstructive pulmonary disease
  • Uncontrolled diabetes mellitus
  • Active viral or bacterial infection
  • Known positive serology for Human immunodeficiency virus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796003

Locations
Japan
Fukuoka, Japan
Hamamatsu, Japan
Hidaka, Japan
Nagasaki, Japan
Nagoya, Japan
Shinjuku, Japan
Tokyo, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided by Janssen Pharmaceutical K.K.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT00796003     History of Changes
Other Study ID Numbers: CR015406, 30979754-JPN-MDS-101
Study First Received: November 20, 2008
Results First Received: May 31, 2013
Last Updated: October 10, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Myelodysplastic syndrome
MDS
Decitabine
JNJ-30979754

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014