Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Antimetabolites

Enzyme Inhibitors

Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days until disease progression (DP), adverse events (AE), withdrawal of consent from further treatment, withdrawal of consent, death, lost to follow-up, or protocol violation.

Subcutaneous administration of azacitidine 75 mg/m\^2/day for 7 days every 28 days optimally for at least 6 cycles until disease progression, unacceptable toxicity, or treatment discontinuation for any other reason

C L Beach

The purpose of the study is to determine whether azacitidine is safe and effective in the treatment of Chinese patients with higher risk Myelodysplastic Syndromes (MDS).

Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome

A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Chinese Subjects With Higher-Risk Myelodysplastic Syndromes

Hematologic Response is defined by those participants who experienced a Complete Response, Partial Response and Stable Disease (SD) based on IWG 2000 response criteria for MDS. 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 • 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 Acute Myelogenous Leukemia.

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 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.

The number of units of platelet transfusions received 56 days prior to treatment, considered the baseline period, (baseline period defined as the screening period before the date of the first dose of azacitidine; any laboratory and blood transfusion data reported on the day of the first dose of azacitidine was considered to be baseline data) and during study was standardized per 28 days and summarized by cycle for platelets. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length.

The number of platelet transfusions received 56 days prior to treatment, considered the baseline period (baseline period defined as the screening period before the date of the first dose of azacitidine; any laboratory and blood transfusion data reported on the day of the first dose of azacitidine was considered to be baseline data) and during study was standardized per 28 days and summarized by cycle for platelets. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length.

The number of units of RBC received 56 days prior to treatment, considered the baseline period (baseline period defined as the screening period before the date of the first dose of azacitidine; any laboratory and blood transfusion data reported on the day of the first dose of azacitidine was considered to be baseline data) and during study was standardized per 28 days and summarized by cycle for RBC. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length.

The number of RBC transfusions received 56 days prior to treatment, considered the baseline period (baseline period defined as the screening period before the date of the first dose of azacitidine; any laboratory and blood transfusion data reported on the day of the first dose of azacitidine was considered to be baseline data) and during study was standardized per 28 days and summarized by cycle for platelets. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length.

The on-treatment adverse event of infection requiring IV antibiotics, antifungals, or antivirals per 28 days/cycle. The overall post-baseline average is the average of number of infections requiring IV antibiotics or IV antiviral per 28 days/cycle.

Overall survival is defined as time to death from any cause, is calculated using date of first dose and date of death, or date of last follow-up for censored participants. Those, who die regardless of the cause of death, will be considered to have an event.

A treatment-emergent adverse events (TEAE) was defined as AEs with an onset date on or after the date of first dose and within 28 days after the date of the last dose. Any AE that occurred beyond this timeframe and was assessed by the investigator as possibly related to study drug was considered treatment-emergent. The intensity and severity of AEs was assessed by the investigator according to the Common Terminology Criteria for Adverse Event (CTCAE) Version 4.0. For any AEs not listed in the CTCAE grading system, the intensities of these events was assessed by the Investigator using the 5-point scale: Grade 1 = Mild, Grade 2 = Moderate; Grade 3 = Severe, Grade 4 = Life threatening, Grade 5 = Death. An SAE is any AE occurring that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and constitutes an important medical event.

Area under the plasma concentration-time curve from time zero to infinity (AUC∞) following multiple doses of Azacitidine on Day 7; if possible, the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration. No AUC extrapolation will be performed with unreliable λz. If % AUC extrapolated is ≥ 25%, AUC∞ will not be reported

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

The observed maximum plasma concentration obtained directly from the observed concentration versus time data.

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.

The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz.

Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞

Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz

Celgene

For extension phase: From 29 December 2014 to 28 days after the date of the last dose of study drug; median treatment duration of any dose of azacitidine was 169 days; range: 7 to 1112 days.

Azacitidine - Parent Phase

Azacitidine 75 mg/m\^2/day subcutaneously for 7 days every 28 days until disease progression (DP), adverse events (AE), withdrawal of consent from further treatment, withdrawal of consent, death, lost to follow-up, or protocol violation

Azacitdine - Extension Phase

Age, Continuous

Sex: Female, Male

The Myelodysplastic Syndrome (MDS) IPSS score assesses the severity of MDS based on 3 prognostic factors each assigned a score: the percentage of bone marrow blasts, chromosome changes in the marrow cells (karyotype) and the presence of one or more low blood cell counts (cytopenias). The IPSS score is the sum of the bone marrow blast + karyotype + cytopenia score and ranges from 0 (low risk) to 3.5 (high risk). Prognosis is categorized as Low risk (score = 0), Intermediate-1 (score 0.5 to 1.0), Intermediate-2 (score 1.5 to 2.0) or High risk (score ≥ 2.5).

International Prognostic Scoring System (IPSS) Risk Classification

FAB is a classification system for five (5) subtypes of myelodysplastic syndrome that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts or a monocytosis. Classification was made by the Local Reviewer.

French-American-British classification (FAB)

The World Health Organization (WHO) classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.

MDS World Health Organization (WHO) Classification

ITT includes all participants who had been screened and enrolled into the study.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Overall CR+PR

Overall CR+PR+SD

Complete Remission (CR)

Partial Remission (PR)

Intent to Treat (ITT) includes all participants who were enrolled into the study.

Percentage of Participants With a Hematologic Response Based on the International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Programmatically Assessed by the Sponsor Using Clinically Relevant Data.

Percentage of Participants With a Hematologic Response Using IWG Criteria for MDS and Assessed by the Investigator

Any improvement

Hematologic Improvement-E (major)

Hematologic Improvement-E (minor)

Hematologic Improvement-P (major)

Hematologic Improvement-P (minor)

Hematologic Improvement-N (major)

Hematologic Improvement-N (minor)

Percentage of Participants Achieving a Hematologic Improvement (HI) Based on 2000 IWG Response Criteria for MDS and Programmatically Assessed by the Sponsor Using Clinically Relevant Data.

Baseline N = 72

Overall Post-Baseline Average N = 72

Overall Change from Baseline N = 72

Cycle 1 N = 72

Cycle 2

Cycle 3

Cycle 4

Cycle 5

Cycle 6

Cycle 7

Cycle 8

Cycle 9

Cycle 10

Cycle 11

Cycle 12

Cycle 13

Cycle 14

Cycle 15

Cycle 16

Cycle 17

Cycle 18

Cycle 19

Cycle 20

Cycle 21

Cycle 22

Cycle 23

Cycle 24

Cycle 25

Cycle 26

Cycle 27

The Number of Units of Platelet Transfusions by Cycle

The Number of Platelet Transfusions by Cycle

Cycle 22 N

ITT includes all participants who were enrolled into the study

The Number of Units of Red Blood Cell (RBC) Transfusions by Cycle

The Number of RBC Transfusions by Cycle

Overall Post Baseline Average N = 72

Overall Change from Baseline N =72

Cycle12

Cycle 14 15

Cycle 26 N

The Number of Infections (Post-baseline Average) Requiring Intravenous (IV) Antibiotics, Anti-fungals, or Antivirals by Cycle

Median OS

25th percentile OS

75th Percentile OS

Kaplan Meier Estimates for Overall Survival (OS)

≥ 1 TEAE

≥ 1 Grade 3 or 4 TEAE

≥ 1 TEAE related to study drug

≥ 1 Grade 3 or 4 TEAE related to study drug

≥ 1 serious TEAE

≥ 1 Grade 3 or 4 serious TEAE

≥ 1 serious TEAE related to study drug

≥ 1 TEAE leading to discontinuation of study drug

≥ 1 TEAE leading to dose reduction of study drug

≥1 TEAE leading to dose interruption of study drug

≥1 TEAE leading to dose reduction/interruption

≥1 TEAE with outcome of death

Safety population included all participants who received at least one dose of azacitidine and had at least one post-dose safety assessment

Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Parent Phase

The PK population includes up to 12 participants with evaluable azacitidine plasma PK profile.

Spots Global Cancer Trial Database for Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial