An Effectiveness and Safety Study of Decitabine in Patients With Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Xian-Janssen Pharmaceutical Ltd.
ClinicalTrials.gov Identifier:
NCT01751867
First received: July 25, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the effectiveness and safety of decitabine in the treatment of myelodysplastic syndrome (name of a group of conditions that occur when the blood-forming cells in the bone marrow are damaged) in Chinese patients.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Decitabine at 15 mg/m2
Drug: Decitabine at 20 mg/m2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Phase IIIb Study for Decitabine in Patients With Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Xian-Janssen Pharmaceutical Ltd.:

Primary Outcome Measures:
  • Overall Response Rate (ORR): Number of Participants Who Achieved Either Complete Remission (CR), Partial Remission (PR), or Marrow Complete Remission (mCR) - International Working Group (IWG) 2006 Response Criteria [ Time Frame: From the date of first dose until 30 to 42 days after the last dose of the 2 years treatment period, or at time of discontinuation ] [ Designated as safety issue: No ]
    IWG 2006 response criteria - CR: bone marrow evaluation shows ≤ 5% blasts; normal maturation of all cells lines (mCR), peripheral blood evaluation shows hemoglobin ≥ 11 g/dL, neutrophils ≥ 1000/mL, platelets ≥ 100,000/mL, 0% blasts; PR: Same as CR, except blasts decrease by ≥ 50%, still greater than 5% in bone marrow.


Secondary Outcome Measures:
  • Hematological Improvement Rate: Number of Participants Who Achieved Complete Remission (CR), Partial Remission (PR) and Hematologic Improvement (HI) - International Working Group (IWG) 2006 Response Criteria [ Time Frame: From the date of first dose until 30 to 42 days after the last dose of the 2 years treatment period, or at time of discontinuation ] [ Designated as safety issue: No ]
    IWG 2006 response criteria - CR: bone marrow evaluation shows ≤ 5% blasts; normal maturation of all cells lines (mCR), peripheral blood evaluation shows hemoglobin ≥ 11 g/dL, neutrophils ≥ 1000/mL, platelets ≥ 100,000/mL, 0% blasts; PR: Same as CR, except blasts decrease by ≥ 50%, still greater than 5% in bone marrow; HI: hemoglobin increase of ≥ 1.5 g/dL, platelet increase of ≥ 30,000/mL (starting with > 20,000/mL), neutrophils increase of ≥ 100% and > 500/μL.

  • Cytogenetic Response Rate: Percentage of Participants Who Achieved Cytogenetic Response (Complete+Partial) by Status of Clinical Overall Response - International Working Group (IWG) 2006 Response Criteria [ Time Frame: From the date of first dose until 30 to 42 days after the last dose of the 2 years treatment period, or at time of discontinuation ] [ Designated as safety issue: No ]
    As per IWG 2006 response criteria - Complete cytogenetic response: disappearance of the chromosomal abnormality without appearance of new ones; Partial cytogenetic response: At least 50% reduction of the chromosomal abnormality. Status of Clinical response - complete remission (CR); marrow CR (mCR); partial remission (PR).

  • Transfusion Independence: Number of Participants Who Were Transfusion Independent [ Time Frame: Baseline; up to 2 years ] [ Designated as safety issue: No ]
    A participant was considered to be transfusion independent, if the participant had no transfusions of Red Blood Cells (RBCs) or platelets for 8 consecutive weeks or more.

  • Mean Percentage of Duration of Hospitalization (Relative to Days on Study Treatment) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Duration of hospitalization was calculated as, total number of days a participant stayed in hospital during study treatment divided by the study treatment duration

  • Overall Survival Rate: Percentage of Participants Who Survived During 6 Months and 12 Months of Treatment. [ Time Frame: From the date of dosing until death or lost to follow-up for up to 2.5 years after last patient was enrolled ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to End of Treatment in Scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ C-30) Physical Functioning Scale [ Time Frame: Baseline to end of treatment (approximately up to 2 years) ] [ Designated as safety issue: No ]
    EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which will be rated on a 7-point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning.


Enrollment: 135
Study Start Date: August 2009
Study Completion Date: April 2013
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3-Day Dose schedule
Decitabine will be administered at a dose of 15 mg/m2 as a continuous intravenous infusion within a 3 hour period, repeated every 8 hours for 3 consecutive days. Cycles will be repeated every 6 weeks.
Drug: Decitabine at 15 mg/m2
Decitabine will be given at a dose of 15 mg/m2 as a continuous intravenous infusion within a 3-hour intravenous infusion, repeated every 8 hours for 3 consecutive days.The total dose per day is 45 mg/m2; The total dose per course is 135 mg/m2. Cycles will be repeated every 6 weeks.
Experimental: 5-Day Dose schedule
Decitabine will be administered at a dose of 20 mg/m2 as a intravenous infusion within 1 hour, once daily for 5 consecutive days. Cycles will be repeated every 4 weeks.
Drug: Decitabine at 20 mg/m2
Decitabine will be given at a dose of 20 mg/m2 as 1-hour IV infusion once daily on Days 1 through 5, of a 4-week treatment cycle.

Detailed Description:

This is a prospective (look forward using periodic observations collected predominantly following patient enrollment), open-label (all people involved in the study know the identity of the assigned drug), Phase IIIb study to evaluate the efficacy and safety of decitabine in the treatment of myelodysplastic syndrome (MDS). Patients are randomized (study drug assigned by chance) in 1:1 ratio to receive treatment with decitabine either 3-day or 5-day course of therapy. When a minimum of 30 patients are reached for 3-day course of therapy, the rest of the patients will all be enrolled into 5-day course of therapy. Each patient in the study treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles. The entire study duration for each patient will be approximately two years. Safety will be evaluated for each patient by monitoring of adverse events, physical examinations, vital signs measurements, electrocardiogram, hematology and clinical chemistry testing.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have diagnosed with Myelodysplastic Syndrome (MDS) denovo (previously not present) or secondary as per the classification of French-American-British (FAB) and International Prognostic Scoring System (IPSS) greater than or eaul to 0.5 as determined by complete blood count (CBC), bone marrow assessment and bone marrow cytogenetics
  • Must have an Eastern Oncology Cooperative Group (ECOG) performance status of 0-2
  • Must have adequate hepatic and renal function as measured by the aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin and serum creatinine, respectively
  • Must have recovered from all toxic effects of prior therapy and not received any chemotherapy for a minimum of 4 weeks (6 weeks if the patient has been treated with a nitrosoureas) prior to the first dose of study drug - Woman must be postmenopausal, or surgically sterile, or abstinent, or, if sexually active, be practicing an effective method of birth control (eg, oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization)

Exclusion Criteria:

  • Must not have a diagnosis of acute myeloid leukemia (greater than 30% bone marrow blasts) - Must not have received radiotherapy within 14 days before the first dose of study drug - Must not have any other prior cancer, other than superficial bladder cancer, basal cell skin and cervical cancer - Must not have associated autoimmune hemolytic anemia or immune thrombocytopenia and inaspirable bone marrow - Must not have a mental illness or any other condition (eg, uncontrolled cardiac or pulmonary disease, diabetes), that could prevent full cooperation with the study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01751867

Locations
China
Beijing, China
Chengdu, China
Guangdong, China
Hangzhou, China
Nanjing, China
Shanghai, China
Suzhou, China
Tianjin, China
Sponsors and Collaborators
Xian-Janssen Pharmaceutical Ltd.
Investigators
Study Director: Xian-Janssen Pharmaceutical Ltd Clinical Trial Xian-Janssen Pharmaceutical Ltd.
  More Information

No publications provided

Responsible Party: Xian-Janssen Pharmaceutical Ltd.
ClinicalTrials.gov Identifier: NCT01751867     History of Changes
Other Study ID Numbers: CR017443, DACOGENMYE-3002
Study First Received: July 25, 2012
Results First Received: June 24, 2013
Last Updated: January 23, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Xian-Janssen Pharmaceutical Ltd.:
Myelodysplastic Syndrome
Dacogen
Oncology
Decitabine
Bone marrow disorders

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 July 22, 2014