Myelodysplastic Syndrome (MDS)Phase 2NCT01599325
Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome
A Phase 2 study testing Azacitidine in people with Myelodysplastic Syndrome (MDS), run by Celgene at 11 sites in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome (MDS)
- What is being tested?
- Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 11 sitesChina
- Study dates
- 24 Jul 2012to 13 Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Chinese males and females of Asian descent ≥ 18 years of age at the time of signing the informed consent document;
- Must have a documented diagnosis of refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T) according to French-American-British (FAB) classification for Myelodysplastic Syndrome (MDS) and with an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk or a diagnosis of myelodysplastic chronic myelomonocytic leukemia (CMML) per modified FAB criteria meeting the following:
- Monocytosis in peripheral blood > 1 x 10^9/L;
- Dysplasia in one or more myeloid cell lines;
- 10% to 29% blasts in the bone marrow; and White blood cell (WBC) count < 13 x 10^9/L
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 ;
- Adequate organ function, defined as:
- Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0 times the ULN;
- Serum Creatinine ≤ 1.5 times the ULN;
- Females of childbearing potential (FCBP) must:
- Agree to the use of a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on azacitidine; and
- for 3 months following the last dose of azacitidine; and have a negative serum pregnancy test within 72 hours prior to starting Investigational Product (IP).
- Male subjects with a female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of azacitidine;
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted;
- Able to adhere to the study visit schedule and other protocol requirements.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Previous treatment with azacitidine or decitabine;
- Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure);
- Uncorrected red cell folate deficiency or vitamin B12 deficiency;
- Diagnosis of metastatic disease;
- Malignant hepatic tumors;
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- Known or suspected hypersensitivity to azacitidine or mannitol;
- Candidate to proceed to bone marrow or stem cell transplant during the study;
- Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS;
- Treatment with erythropoietin or myeloid growth factors (granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]) during the 21 days prior to Day 1 of Cycle 1;
- Treatment with androgenic hormones during the 14 days prior to Day 1 of Cycle 1;
- Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C;
- Treatment with other investigational drugs, including thalidomide and arsenic trioxide, 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; and
- Pregnant or lactating females;
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study;
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study;
- Any condition that confounds the ability to interpret data from the study.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
China11 sites
Peking University People's Hospital
Beijing, 100044
The 301 Hospital- Chinese PLA General Hospital
Beijing, 300200
The Third Hospital of Peking University
Beijing
West China Hospital of Sichuan University
Chengdu, 610041
Guangdong General Hospital
Guangzhou, 510080
1st Hospital Zhejiang University (The First Affiliated Hospital of Zhejiang University )
Hangzhou, 310003
Ruijin Hospital Shanghai Jiaotong University
Shanghai, 200025
Shanghai 6th Hospital
Shanghai, 200233
The 1st Hospital of Soochow University
Suzhou, 215006
Blood Disease Hospital, Chinese Academy of Medical Science and Peking Union Medical College
Tianjin, 300041
Wuhan Union Hospital
Wuhan, 430000
About this study
Official title: 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
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).
- Conditions
- Myelodysplastic Syndrome (MDS)
- Being tested
- Azacitidine
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza
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
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine | Experimental | 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. Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
Percentage of Participants With a Hematologic Response Using IWG Criteria for MDS and Assessed by the Investigator
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.
Measured: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
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.
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.
Measured: Up to 29 January 2015; 894 days
Secondary outcomes (15)
The Number of Units of Platelet Transfusions by Cycle
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.
Measured: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Platelet Transfusions by Cycle
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.
Measured: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Units of Red Blood Cell (RBC) Transfusions by Cycle
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.
Measured: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of RBC Transfusions by Cycle
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.
Measured: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Infections (Post-baseline Average) Requiring Intravenous (IV) Antibiotics, Anti-fungals, or Antivirals by Cycle
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.
Measured: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
Kaplan Meier Estimates for Overall Survival (OS)
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.
Measured: Until the end of the survival follow-up period; Up to data cut-off of 29 January 2015; 894 days
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Parent Phase
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.
Measured: Up to 29 January 2015; from the first dose of study drug to 28 days after the date of the last dose of study drug (maximum time on study was 244 days)
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine
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
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine
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.
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Maximum Observed Plasma Concentration (Cmax) of Azacitidine
The observed maximum plasma concentration obtained directly from the observed concentration versus time data.
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Time to Maximum Plasma Concentration (Tmax) of Azacitidine
Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Terminal Phase of Half-life (T1/2) of Azacitidine
The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz.
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Apparent Total Plasma Clearance (CL/F) of Azacitidine
Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Apparent Volume of Distribution (Vd/F) of Azacitidine
Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz
Measured: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Extension Phase
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.
Measured: Up to final data cut off date of 25 April 2018; from the first dose of study drug extesnion of 29 December 2014 to 28 days after the date of the last dose of study drug; median duration of any dose of study drug was 169 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2012 (estimated)
- Study start24 Jul 2012
- Primary completion29 Jan 2015
- Study completion13 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- C L Beach, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01599325
- Sponsor's protocol ID
- AZA-MDS-002
- Status last verified
- Mar 2019
- First submitted
- 14 May 2012
- Last updated
- 19 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01599325
- Acronym / sponsor ID
- AZA-MDS-002
- Conditions
- Myelodysplastic Syndrome (MDS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 24 Jul 2012 (actual)
- Primary completion
- 29 Jan 2015 (actual)
- Study completion
- 13 Mar 2018 (actual)
- First posted
- 16 May 2012 (estimated)
- Results
- Posted 29 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine | Experimental | Drug: AzacitidineAzacitidine 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Chinese males and females of Asian descent ≥ 18 years of age at the time of signing the informed consent document;
- Must have a documented diagnosis of refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T) according to French-American-British (FAB) classification for Myelodysplastic Syndrome (MDS) and with an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk or a diagnosis of myelodysplastic chronic myelomonocytic leukemia (CMML) per modified FAB criteria meeting the following:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 ;
- Adequate organ function, defined as:
- Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
Key exclusion criteria (17 listed)
- Previous treatment with azacitidine or decitabine;
- Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure);
- Uncorrected red cell folate deficiency or vitamin B12 deficiency;
- Diagnosis of metastatic disease;
- Malignant hepatic tumors;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: VidazaSubcutaneous 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 | Drug | Azacitidine |
Primary outcome
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.
Time frame: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
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.
Percentage of Participants With a Hematologic Response Using IWG Criteria for MDS and Assessed by the Investigator
Time frame: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
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.
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.
Time frame: Up to 29 January 2015; 894 days
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.
15 secondary outcomes
The Number of Units of Platelet Transfusions by Cycle
Time frame: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Platelet Transfusions by Cycle
Time frame: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Units of Red Blood Cell (RBC) Transfusions by Cycle
Time frame: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of RBC Transfusions by Cycle
Time frame: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
The Number of Infections (Post-baseline Average) Requiring Intravenous (IV) Antibiotics, Anti-fungals, or Antivirals by Cycle
Time frame: Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days
Kaplan Meier Estimates for Overall Survival (OS)
Time frame: Until the end of the survival follow-up period; Up to data cut-off of 29 January 2015; 894 days
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Parent Phase
Time frame: Up to 29 January 2015; from the first dose of study drug to 28 days after the date of the last dose of study drug (maximum time on study was 244 days)
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Maximum Observed Plasma Concentration (Cmax) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Time to Maximum Plasma Concentration (Tmax) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Terminal Phase of Half-life (T1/2) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Apparent Total Plasma Clearance (CL/F) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Apparent Volume of Distribution (Vd/F) of Azacitidine
Time frame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Extension Phase
Time frame: Up to final data cut off date of 25 April 2018; from the first dose of study drug extesnion of 29 December 2014 to 28 days after the date of the last dose of study drug; median duration of any dose of study drug was 169 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C L Beach study director
Celgene
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine in people with Myelodysplastic Syndrome (MDS), run by Celgene at 11 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2019.