Clinical trial NCT01201811: Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2010-09-15
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Primary outcomes:
measure: Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator
timeFrame: Response assessed at end of cycle 6; through week 24; End of study
measure: Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor
timeFrame: Response assessed at end of cycle 6; through week 24; End of study
Secondary outcomes:
measure: Number of Red Blood Cell (RBC) Transfusions by Cycle
timeFrame: Up to week 24;The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
measure: Number of Platelet Transfusions by Cycle
timeFrame: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
measure: Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days
timeFrame: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
measure: Number of Participants With Adverse Events (AE)
timeFrame: From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Time to Maximum Plasma Concentration (Tmax) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Terminal Phase of Half-life (T1/2) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Apparent Total Plasma Clearance (CL/F) of Azacitidine
timeFrame: Timeframe: Days 5 and 6 at predose and Day 7 (pre-dose) at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
measure: Apparent Volume of Distribution (Vd/F) of Azacitidine
timeFrame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose
Other outcomes:
measure: Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
timeFrame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit
measure: Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
timeFrame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
measure: Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
timeFrame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
measure: Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
timeFrame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.
Locations:
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Chiayi
country: Taiwan
facility: Chiayi Chang Gung Memorial Hospital
city: Hualien
country: Taiwan
facility: Buddhist Tzu Chi General Hospital-Hualien Tzu Chi Medical Center
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical Hospital University
city: New Taipei City
country: Taiwan
facility: Shuang-ho Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: Celgene
name: C L Beach, PharmD
role: STUDY_DIRECTOR
References:
citation: Chou WC, Yeh SP, Hsiao LT, Lin SF, Chen YC, Chen TY, Laille E, Galettis A, Dong Q, Songer S, Beach CL. Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Asia Pac J Clin Oncol. 2017 Oct;13(5):e430-e439. doi: 10.1111/ajco.12659. Epub 2017 Jan 25.