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

NCT01201811 | Completed Phase 4 Results

• 1 other identifier: AZA-MDS-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 11

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).

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator

  Hematologic Response according to the 2000 International Working Group (IWG) response criteria for MDS was based on the Investigators determination and defined as: * Complete Response (CR): repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia * Partial Response (PR): same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment * Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months. * Failure: death during treatment or disease progression * Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence * Disease Progression: change in blast levels * Disease Transformation to AML

  Response assessed at end of cycle 6; through week 24; End of study

• 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

  Hematologic improvements (HI) have 4 categories: 1. Erythroid response (HI-E): Major \>20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements. 2. Platelet response (HI-P): Major absolute increase of ≥30x10\^9/L or platelet transfusion independence. Minor-≥50% increase. 3. Neutrophil response (HI-N): Major 100% increase or an absolute increase of \>0.5x10\^9/L. Minor-≥100% increase and absolute increase of \<0.5x10\^9/L 4. Progression or relapse after HI Overall hematological improvement (HI) was defined as any type (major or minor) of improvement of HI-E, HI-P, or HI-N. Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Sponsor's determination was derived using clinically relevant data. Denominator for progression/relapse after HI included participants who had achieved HI.

  Response assessed at end of cycle 6; through week 24; End of study

Secondary Outcomes (11)

• Number of Red Blood Cell (RBC) Transfusions by Cycle

  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.

• Number of Platelet Transfusions by Cycle

  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.

• Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days

  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.

• Number of Participants With Adverse Events (AE)

  From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine

  Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Other Outcomes (4)

• Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline

  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

• Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline

  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.

• Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline

  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.

Study Arms (1)

Single-Arm

EXPERIMENTAL

Azacitidine 75 mg/m\^2/day Subcutaneous for 7 days Day every 28 days for up to 6 cycles

Drug: Azacitidine

Interventions

Azacitidine DRUG

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.

Single-Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (11)

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Chiayi Chang Gung Memorial Hospital

Chiayi City, 613, Taiwan

Location

Buddhist Tzu Chi General Hospital-Hualien Tzu Chi Medical Center

Hualien City, 970, Taiwan

Location

Kaohsiung Medical Hospital University

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

Shuang-ho Hospital

New Taipei City, 23561, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 28124500 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes; Pathologic Processes; Neoplasms; Bone Marrow Diseases; Hematologic Diseases

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• C L Beach, PharmD

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 15, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: December 5, 2019
• Results First Posted: June 24, 2014

Record last verified: 2019-11

Locations

TW (11)