Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01201811
First received: September 13, 2010
Last updated: August 14, 2013
Last verified: August 2013
  Purpose

The primary purpose of this study is to determine the effectiveness and safety of azacitidine in the treatment of Taiwanese subjects with higher-risk Myelodysplastic Syndrome (MDS).


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: Azacitidine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 4, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Proportion of participants with a hematologic response (defined as Complete Response and Partial Response), and Hematologic Improvement based on International Working Group 2000 response criteria for Myelodysplastic Syndromes. [ Time Frame: 7 months ] [ Designated as safety issue: No ]
    Proportion of participants with a hematologic response (defined as Complete Response and Partial Response), and Hematologic Improvement based on International Working Group 2000 response criteria for Myelodysplastic Syndromes.


Secondary Outcome Measures:
  • Number of red blood cell transfusions [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • Number of platelet transfusions [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • Number of infections requiring intravenous antibiotics [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • Safety (type, frequency, severity, and relationship of adverse events to azacitidine) [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
  • Steady-state plasma azacitidine concentrations [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: October 2010
Estimated Study Completion Date: September 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-Arm
Azacitidine 75 mg/m^2/day Subcutaneous for 7 days Day every 28 days for up to 6 cycles
Drug: Azacitidine
Subjects will receive azacitidine 75 mg/m2/day SC for 7 days every 28 days for up to 6 cycles, unless they are discontinued from the treatment. In addition, subjects may receive best supportive care as needed, including antibiotics and transfusions, per Investigator discretion.

Detailed Description:

The study has 3 phases which include the Screening Phase, the Treatment Phase, and the Post-Treatment Phase and outlined as follows:

Screening Phase:

Subjects will provide informed consent prior to undergoing any study-related procedures. Screening procedures are to take place within 28 days prior to the initiation of azacitidine treatment (Day 1, Cycle 1). Subject eligibility will be based on central pathology review. Bone marrow aspirate and bone marrow biopsy will be collected at screening and sent for morphological assessment by a central pathology reviewer prior to the subject receiving IP. The central pathology reviewer will document the MDS classification according to the FAB and WHO criteria (Appendix A and B, respectively).

A standard cytogenetic metaphase preparation will be prepared from the bone marrow aspirate and sent to the local or central laboratory (for sites without local analysis capability) for the cytogenetic analysis prior to receiving IP.

The IPSS score will be calculated using the central reviewer's pathology report for bone marrow blast percentage, local cytogenetic assessment for karyotype, and central laboratory report for number of cytopenias (Appendix D).

Treatment Phase:

The first dose of azacitidine for each subject begins on Day 1 of Cycle 1. All subjects will receive azacitidine 75 mg/m2/day SC for 7 days every 28 days for up to 6 cycles, unless they are discontinued from treatment. Visits during the treatment phase are to be scheduled weekly for the first 2 cycles, then every other week for all subsequent cycles throughout the rest of the study. Safety and efficacy measures are to be performed weekly, every other week, every 4 weeks, or at 24 weeks, depending on the procedure.

Post-Treatment Phase:

All discontinued subjects, regardless of reason for discontinuation, should undergo end-of-study procedures at the time of study discontinuation. Subjects will have a follow-up visit for the collection of adverse events up to 28 days after last IP dose.

  Eligibility

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

Inclusion Criteria:

  • A diagnosis of RAEB or RAEB-T according to FAB classification for MDS and with an IPSS score of intermediate-2 or high risk or a diagnosis of myelodysplastic CMML per modified FAB criteria.
  • Taiwanese males and females ≥ 18 years of age
  • ECOG 0, 1, or 2;
  • Adequate hepatic and renal organ function

Exclusion Criteria:

  • Previous treatment with azacitidine or decitabine
  • Malignant disease diagnosed within prior 12 months
  • Uncorrected red cell folate deficiency or vitamin B12 deficiency
  • Diagnosis of metastatic disease
  • Malignant hepatic tumors
  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS
  • Treatment with erythropoietin or myeloid growth factors during the 21 days prior to Day 1 of Cycle 1 or androgenic hormones during the 14 days prior to Day 1 of Cycle 1;
  • Active HIV or viral hepatitis type B or C
  • Treatment with other investigational drugs within the previous 30 days prior to Day 1 of Cycle 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period;
  • Pregnant or lactating females
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01201811

Locations
Taiwan
Changhua Christian Hospital
Changhua, Taiwan, 500
Chiayi Chang Gung Memorial Hospital
Chiayi, Taiwan, 613
Buddhist Tzu Chi General Hospital-Hualien Tzu Chi Medical Center
Hualien, Taiwan, 970
Kaohsiung Medical Hospital University
Kaohsiung, Taiwan, 807
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Taiwan, 833
Shuang-ho Hospital
New Taipei City, Taiwan, 23561
China Medical University Hospital
Taichung, Taiwan, 404
National Cheng Kung University Hospital
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 10002
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
Tri-Service General Hospital
Taipei, Taiwan, 11490
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: C L Beach, PharmD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01201811     History of Changes
Other Study ID Numbers: AZA-MDS-001
Study First Received: September 13, 2010
Last Updated: August 14, 2013
Health Authority: Taiwan : Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Myelodysplastic Syndromes
Taiwan
Azacitidine
Vidaza
Celgene
Pathologic Processes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Enzyme inhibitors

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

ClinicalTrials.gov processed this record on April 15, 2014