Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator [Response assessed at end of cycle 6; through week 24; End of study]
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
- 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 [Response assessed at end of cycle 6; through week 24; End of study]
Hematologic improvements (HI) have 4 categories: Erythroid response (HI-E): Major >20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements. Platelet response (HI-P): Major absolute increase of ≥30x10^9/L or platelet transfusion independence. Minor-≥50% increase. 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 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.
Secondary Outcome Measures
- 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.]
The number of transfusions received 56 days prior to treatment and during study were standardized per 28 days and summarized by cycle for RBCs. 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. For each participant the overall post-baseline average was calculated as the average of # of RBC transfusions per cycle.
- 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.]
The number of transfusions received 56 days prior to treatment 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. For each participant the overall post-baseline average was calculated as the average of # of platelet transfusions per cycle.
- 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.]
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. For each participant the overall post-baseline average was calculated as the average of # of infections requiring IV antibiotics or IV antiviral per 28 days per cycle.
- 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)]
An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE): Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Treatment Emergent AEs (TEAE) were defined as AEs with an onset date on or after the first dose of study drug and within 28 days after the date of the last dose. In addition, any AE that occurred beyond this timeframe and that was assessed by the investigator as possibly related to study drug was considered a TEAE.
- 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]
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 was performed with unreliable λz. If % AUC extrapolated is ≥ 25%, AUC∞ was not reported.
- Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine [Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]
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.
- Maximum Observed Plasma Concentration (Cmax) of Azacitidine [Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]
The observed maximum plasma concentration obtained directly from the observed concentration versus time data.
- Time to Maximum Plasma Concentration (Tmax) of Azacitidine [Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]
Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.
- Terminal Phase of Half-life (T1/2) of Azacitidine [Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]
The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz.
- Apparent Total Plasma Clearance (CL/F) of Azacitidine [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]
Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞
- Apparent Volume of Distribution (Vd/F) of Azacitidine [Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]
Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz
Other Outcome Measures
- 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]
A participant was considered transfusion dependent at baseline if the participant had one or more Red Blood Cell transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no transfusions during any 56 consecutive days or more (e.g., Day 1 through 56, Day 2 through 57, etc). Otherwise, they were considered transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)
- 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.]
A participant was considered RBC transfusion-independent at baseline if the participant had no RBC transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no RBC transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)
- 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.]
A participant was considered platelet transfusion dependent at baseline if the participant had one or more platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)
- Participants' Platelet 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.]
A participant was considered platelet transfusion independent at baseline if the participant had no platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Changhua Christian Hospital | Changhua | Taiwan | 500 | |
| 2 | Chiayi Chang Gung Memorial Hospital | Chiayi | Taiwan | 613 | |
| 3 | Buddhist Tzu Chi General Hospital-Hualien Tzu Chi Medical Center | Hualien | Taiwan | 970 | |
| 4 | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | Taiwan | 833 | |
| 5 | Kaohsiung Medical Hospital University | Kaohsiung | Taiwan | 807 | |
| 6 | Shuang-ho Hospital | New Taipei City | Taiwan | 23561 | |
| 7 | China Medical University Hospital | Taichung | Taiwan | 404 | |
| 8 | National Cheng Kung University Hospital | Tainan | Taiwan | 704 | |
| 9 | National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
| 10 | Taipei Veterans General Hospital | Taipei | Taiwan | 11217 | |
| 11 | Tri-Service General Hospital | Taipei | Taiwan | 11490 |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: C L Beach, PharmD, Celgene
Study Documents (Full-Text)
None provided.More Information
Publications
- AZA-MDS-001
Study Results
Participant Flow
| Recruitment Details | The study was conducted at nine investigational sites within Taiwan. The purpose of the current study was to evaluate the efficacy, safety, and steady-state Pharmacokinetic (PK) profile of subcutaneous (SC) azacitidine given at a dose of 75 mg/m^2/day for 7 days in Taiwanese participants with higher-risk Myelodysplastic Syndrome (MDS). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Period Title: Overall Study | |
| STARTED | 44 |
| COMPLETED | 25 |
| NOT COMPLETED | 19 |
Baseline Characteristics
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Overall Participants | 44 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
62.3
(11.76)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
17
38.6%
|
| Male |
27
61.4%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Asian |
44
100%
|
| Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification (Count of Participants) | |
| Refractory anemia with excess blasts (RAEB) |
35
79.5%
|
| RAEB in transformation |
7
15.9%
|
| Chronic myelomonocytic leukemia (Modified CMML) |
2
4.5%
|
| Acute myelogenous leukemia (AML) |
0
0%
|
| World Health Organization (WHO) Classification (Count of Participants) | |
| Refractory anemia with excess blasts (RAEB-1) |
15
34.1%
|
| Refractory anemia with excess blasts (RAEB-2) |
23
52.3%
|
| Acute myelogenous leukemia (AML) |
5
11.4%
|
| Chronic myelomonocytic leukemia (CMML -1) |
1
2.3%
|
| Chronic myelomonocytic leukemia (CMML-2) |
0
0%
|
| Refractory anemia (RA) |
0
0%
|
| RA with ringed sideroblasts (RARS) |
0
0%
|
| Refractory Cytopenia Multilineage Dysplasia (RCMD) |
0
0%
|
| Myelodysplastic Syndrome - Unclassified (MDS-U) |
0
0%
|
| International Prognostic Scoring System (IPSS) (Count of Participants) | |
| Low risk (0) |
0
0%
|
| Intermediate-1 (0.5 - 1.0) |
2
4.5%
|
| Intermediate-2 (1.5 - 2.0) |
16
36.4%
|
| High Risk (≥ 2.5) |
26
59.1%
|
Outcome Measures
| Title | Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator |
|---|---|
| Description | 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 |
| Time Frame | Response assessed at end of cycle 6; through week 24; End of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population was defined as all enrolled participants |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| Overall (CR+PR) |
0
0%
|
| Overall (CR+PR+SD) |
63.6
144.5%
|
| Complete Remission (CR) |
0.0
0%
|
| Partial Remission (PR) |
0.0
0%
|
| Stable Disease (SD) |
63.6
144.5%
|
| Disease Progression (DP) |
2.3
5.2%
|
| Transformation to AML |
4.5
10.2%
|
| Failure |
4.5
10.2%
|
| No Response Assessed |
25.0
56.8%
|
| Title | 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 |
|---|---|
| Description | Hematologic improvements (HI) have 4 categories: Erythroid response (HI-E): Major >20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements. Platelet response (HI-P): Major absolute increase of ≥30x10^9/L or platelet transfusion independence. Minor-≥50% increase. 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 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. |
| Time Frame | Response assessed at end of cycle 6; through week 24; End of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population was defined as all enrolled participants |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| Any improvement |
50.0
113.6%
|
| Hematologic Improvement-E (major) |
31.8
72.3%
|
| Hematologic Improvement-E (minor) |
9.1
20.7%
|
| Hematologic Improvement-P (major) |
37.8
85.9%
|
| Hematologic Improvement-P (minor) |
0
0%
|
| Hematologic Improvement-N (major) |
7.1
16.1%
|
| Hematologic Improvement-N (minor) |
0
0%
|
| Progression/relapse after HI |
27.3
62%
|
| Title | Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline |
|---|---|
| Description | A participant was considered transfusion dependent at baseline if the participant had one or more Red Blood Cell transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no transfusions during any 56 consecutive days or more (e.g., Day 1 through 56, Day 2 through 57, etc). Otherwise, they were considered transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12) |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) participants who were transfusion dependent |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 32 |
| Baseline Dependent: On-Treatment Independent |
37.5
(1.97)
85.2%
|
| Baseline Dependent; On-Treatment Dependent |
62.5
(2.47)
142%
|
| Title | Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline |
|---|---|
| Description | A participant was considered RBC transfusion-independent at baseline if the participant had no RBC transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no RBC transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12) |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent to Treat (ITT) participants who were transfusion independent |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Baseline Independent; On-Treatment Independent |
75.0
170.5%
|
| Baseline Independent; On-Treatment Dependent |
25.0
56.8%
|
| Title | Number of Red Blood Cell (RBC) Transfusions by Cycle |
|---|---|
| Description | The number of transfusions received 56 days prior to treatment and during study were standardized per 28 days and summarized by cycle for RBCs. 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. For each participant the overall post-baseline average was calculated as the average of # of RBC transfusions per cycle. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population- The intent-to-treat (ITT) population was defined as all enrolled participants. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| Baseline (N = 44) |
1.3
(1.97)
|
| Overall Post-Baseline Average (N = 44) |
2.4
(2.47)
|
| overall Change from Baseline ( N = 44) |
1.0
(2.59)
|
| Cycle 1 ( N = 44) |
2.5
(2.27)
|
| Cycle 2 |
2.3
(2.03)
|
| Cycle 3 |
2.2
(2.90)
|
| Cycle 4 |
1.5
(2.11)
|
| Cycle 5 |
1.4
(2.59)
|
| Cycle 6 |
1.9
(3.96)
|
| Title | Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline |
|---|---|
| Description | A participant was considered platelet transfusion dependent at baseline if the participant had one or more platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26) |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population who were transfusion dependent |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 18 |
| Baseline Dependent; On-Treatment Independent |
38.9
88.4%
|
| Baseline Dependent; On-Treatment Dependent |
61.1
138.9%
|
| Title | Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline |
|---|---|
| Description | A participant was considered platelet transfusion independent at baseline if the participant had no platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent. The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26) |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) participants who were transfusion independent |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 26 |
| Baseline Independent: On-Treatment Independent |
76.9
|
| Baseline Independent; On-Treatment Dependent |
23.1
|
| Title | Number of Platelet Transfusions by Cycle |
|---|---|
| Description | The number of transfusions received 56 days prior to treatment 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. For each participant the overall post-baseline average was calculated as the average of # of platelet transfusions per cycle. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population was defined as all enrolled participants. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| Baseline ( N = 44) |
0.9
(2.40)
|
| Overall Post-Baseline Average ( N= 44) |
2.7
(3.56)
|
| OverallChange from Baseline ( N = 44) |
1.8
(3.53)
|
| Cycle 1 ( N = 44) |
2.6
(3.38)
|
| Cycle 2 |
2.3
(3.28)
|
| Cycle 3 |
3.0
(4.85)
|
| Cycle 4 |
1.6
(2.89)
|
| Cycle 5 |
1.9
(3.61)
|
| Cycle 6 |
2.7
(6.01)
|
| Title | Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days |
|---|---|
| Description | 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. For each participant the overall post-baseline average was calculated as the average of # of infections requiring IV antibiotics or IV antiviral per 28 days per cycle. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population was defined as all enrolled participants. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| Baseline |
0.1
(0.51)
|
| Overall Post Baseline |
0.5
(0.79)
|
| Overall Change from Baseline |
0.4
(0.98)
|
| Cycle 1 |
0.5
(0.85)
|
| Cycle 2 |
0.4
(0.61)
|
| Cycle 3 |
0.4
(0.82)
|
| Cycle 4 |
0.1
(0.39)
|
| Cycle 5 |
0.1
(0.38)
|
| Cycle 6 |
0.2
(0.66)
|
| Title | Number of Participants With Adverse Events (AE) |
|---|---|
| Description | An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE): Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Treatment Emergent AEs (TEAE) were defined as AEs with an onset date on or after the first dose of study drug and within 28 days after the date of the last dose. In addition, any AE that occurred beyond this timeframe and that was assessed by the investigator as possibly related to study drug was considered a TEAE. |
| Time Frame | From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included enrolled participants who received at least one dose of investigational product and had at least one postdose assessment |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 44 |
| ≥ 1 TEAE |
44
100%
|
| ≥ 1 NCI Grade 3 or 4 TEAE |
37
84.1%
|
| ≥ TEAE related to study drug |
34
77.3%
|
| ≥ 1 NCI Grade 3 or 4 TEAE related to study drug |
22
50%
|
| ≥ 1 serious TEAE |
28
63.6%
|
| ≥ 1 NCI CTC Grade 3 or 4 serious TEAE |
24
54.5%
|
| ≥ 1 serious TEAE related to study drug |
14
31.8%
|
| TEAE leading to discontinuation of study drug |
8
18.2%
|
| TEAE leading to study drug dose reduction |
7
15.9%
|
| TEAE leading to study drug dose interruption |
16
36.4%
|
| TEAE leading to dose reduction or interruption |
20
45.5%
|
| TEAE leading to death |
7
15.9%
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine |
|---|---|
| Description | 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 was performed with unreliable λz. If % AUC extrapolated is ≥ 25%, AUC∞ was not reported. |
| Time Frame | Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
859.1
(23.4)
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine |
|---|---|
| Description | 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. |
| Time Frame | Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
852.8
(23.3)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Azacitidine |
|---|---|
| Description | The observed maximum plasma concentration obtained directly from the observed concentration versus time data. |
| Time Frame | Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
972.3
(44.0)
|
| Title | Time to Maximum Plasma Concentration (Tmax) of Azacitidine |
|---|---|
| Description | Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data. |
| Time Frame | Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
0.29
(27.65)
|
| Title | Terminal Phase of Half-life (T1/2) of Azacitidine |
|---|---|
| Description | The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz. |
| Time Frame | Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
1.0
(38.7)
|
| Title | Apparent Total Plasma Clearance (CL/F) of Azacitidine |
|---|---|
| Description | Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞ |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
149.6
(29.6)
|
| Title | Apparent Volume of Distribution (Vd/F) of Azacitidine |
|---|---|
| Description | Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz |
| Time Frame | Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population includes all participants with evaluable azacitidine plasma PK profile. |
| Arm/Group Title | Azacitidine |
|---|---|
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles |
| Measure Participants | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters] |
205.3
(32.4)
|
Adverse Events
| Time Frame | From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days) | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Azacitidine | |
| Arm/Group Description | Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles | |
All Cause Mortality |
||
| Azacitidine | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Azacitidine | ||
| Affected / at Risk (%) | # Events | |
| Total | 28/44 (63.6%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/44 (2.3%) | |
| Febrile neutropenia | 10/44 (22.7%) | |
| Neutropenia | 3/44 (6.8%) | |
| Splenic infarction | 1/44 (2.3%) | |
| Thrombocytopenia | 2/44 (4.5%) | |
| Cardiac disorders | ||
| Cardiac arrest | 1/44 (2.3%) | |
| Cardiac failure congestive | 1/44 (2.3%) | |
| Gastrointestinal disorders | ||
| Caecitis | 1/44 (2.3%) | |
| Colitis | 1/44 (2.3%) | |
| Enteritis | 1/44 (2.3%) | |
| Gastrointestinal haemorrhage | 1/44 (2.3%) | |
| Ileitis | 1/44 (2.3%) | |
| Pancreatitis acute | 1/44 (2.3%) | |
| General disorders | ||
| Pyrexia | 6/44 (13.6%) | |
| Hepatobiliary disorders | ||
| Cholecystitis acute | 1/44 (2.3%) | |
| Hepatic failure | 1/44 (2.3%) | |
| Infections and infestations | ||
| Abdominal infection | 1/44 (2.3%) | |
| Anal abscess | 1/44 (2.3%) | |
| Appendicitis | 1/44 (2.3%) | |
| Biliary tract infection | 1/44 (2.3%) | |
| Cellulitis | 2/44 (4.5%) | |
| Enterobacter infection | 1/44 (2.3%) | |
| Epiglottitis | 1/44 (2.3%) | |
| Liver abscess | 1/44 (2.3%) | |
| Pneumonia | 8/44 (18.2%) | |
| Postoperative wound infection | 2/44 (4.5%) | |
| Sepsis | 4/44 (9.1%) | |
| Septic shock | 2/44 (4.5%) | |
| Soft tissue infection | 1/44 (2.3%) | |
| Subdiaphragmatic abscess | 1/44 (2.3%) | |
| Injury, poisoning and procedural complications | ||
| Procedural pain | 1/44 (2.3%) | |
| Subdural haemorrhage | 1/44 (2.3%) | |
| Investigations | ||
| Alanine aminotransferase increased | 1/44 (2.3%) | |
| Aspartate aminotransferase increased | 1/44 (2.3%) | |
| Metabolism and nutrition disorders | ||
| Hyperglycaemic hyperosmolar nonketotic syndrome | 1/44 (2.3%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 1/44 (2.3%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Acute monocytic leukaemia | 1/44 (2.3%) | |
| Tumour associated fever | 1/44 (2.3%) | |
| Nervous system disorders | ||
| Cerebellar haemorrhage | 1/44 (2.3%) | |
| Haemorrhage intracranial | 3/44 (6.8%) | |
| Sciatica | 1/44 (2.3%) | |
| Renal and urinary disorders | ||
| Renal failure acute | 1/44 (2.3%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Acute pulmonary oedema | 1/44 (2.3%) | |
| Acute respiratory failure | 3/44 (6.8%) | |
| Pleural effusion | 1/44 (2.3%) | |
| Pneumonia aspiration | 1/44 (2.3%) | |
| Pneumonitis | 1/44 (2.3%) | |
| Respiratory failure | 1/44 (2.3%) | |
| Vascular disorders | ||
| Hypotension | 1/44 (2.3%) | |
Other (Not Including Serious) Adverse Events |
||
| Azacitidine | ||
| Affected / at Risk (%) | # Events | |
| Total | 44/44 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 19/44 (43.2%) | |
| Febrile neutropenia | 8/44 (18.2%) | |
| Leukopenia | 19/44 (43.2%) | |
| Neutropenia | 23/44 (52.3%) | |
| Thrombocytopenia | 16/44 (36.4%) | |
| Eye disorders | ||
| Conjunctivitis | 4/44 (9.1%) | |
| Dry eye | 3/44 (6.8%) | |
| Gastrointestinal disorders | ||
| Abdominal distension | 7/44 (15.9%) | |
| Abdominal pain upper | 3/44 (6.8%) | |
| Constipation | 17/44 (38.6%) | |
| Diarrhoea | 17/44 (38.6%) | |
| Dyspepsia | 3/44 (6.8%) | |
| Gingival bleeding | 8/44 (18.2%) | |
| Haemorrhoids | 8/44 (18.2%) | |
| Lip ulceration | 3/44 (6.8%) | |
| Melaena | 3/44 (6.8%) | |
| Mouth ulceration | 7/44 (15.9%) | |
| Nausea | 17/44 (38.6%) | |
| Stomatitis | 4/44 (9.1%) | |
| Vomiting | 17/44 (38.6%) | |
| General disorders | ||
| Asthenia | 6/44 (13.6%) | |
| Fatigue | 9/44 (20.5%) | |
| Feeling cold | 3/44 (6.8%) | |
| Injection site pain | 5/44 (11.4%) | |
| Malaise | 3/44 (6.8%) | |
| Non-cardiac chest pain | 5/44 (11.4%) | |
| Oedema peripheral | 6/44 (13.6%) | |
| Pyrexia | 23/44 (52.3%) | |
| Infections and infestations | ||
| Gingivitis | 3/44 (6.8%) | |
| Nasopharyngitis | 3/44 (6.8%) | |
| Oral candidiasis | 3/44 (6.8%) | |
| Periodontitis | 3/44 (6.8%) | |
| Pneumonia | 7/44 (15.9%) | |
| Injury, poisoning and procedural complications | ||
| Allergic transfusion reaction | 3/44 (6.8%) | |
| Procedural pain | 3/44 (6.8%) | |
| Transfusion reaction | 7/44 (15.9%) | |
| Investigations | ||
| Alanine aminotransferase increased | 6/44 (13.6%) | |
| Aspartate aminotransferase increased | 3/44 (6.8%) | |
| Weight decreased | 3/44 (6.8%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 12/44 (27.3%) | |
| Haemochromatosis | 3/44 (6.8%) | |
| Hypoalbuminaemia | 4/44 (9.1%) | |
| Hypocalcaemia | 3/44 (6.8%) | |
| Hypokalaemia | 13/44 (29.5%) | |
| Hyponatraemia | 5/44 (11.4%) | |
| Musculoskeletal and connective tissue disorders | ||
| Myalgia | 4/44 (9.1%) | |
| Pain in extremity | 5/44 (11.4%) | |
| Nervous system disorders | ||
| Dizziness | 17/44 (38.6%) | |
| Headache | 8/44 (18.2%) | |
| Psychiatric disorders | ||
| Insomnia | 9/44 (20.5%) | |
| Renal and urinary disorders | ||
| Haematuria | 3/44 (6.8%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 22/44 (50%) | |
| Dyspnoea | 8/44 (18.2%) | |
| Dyspnoea exertional | 6/44 (13.6%) | |
| Epistaxis | 4/44 (9.1%) | |
| Nasal congestion | 3/44 (6.8%) | |
| Oropharyngeal pain | 4/44 (9.1%) | |
| Pleural effusion | 4/44 (9.1%) | |
| Productive cough | 4/44 (9.1%) | |
| Rhinorrhoea | 10/44 (22.7%) | |
| Skin and subcutaneous tissue disorders | ||
| Ecchymosis | 7/44 (15.9%) | |
| Petechiae | 4/44 (9.1%) | |
| Pruritus | 11/44 (25%) | |
| Rash | 9/44 (20.5%) | |
| Rash pruritic | 3/44 (6.8%) | |
| Vascular disorders | ||
| Hypertension | 4/44 (9.1%) | |
| Hypotension | 3/44 (6.8%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Multicenter publication must include input from all Investigators involved in the study and Sponsor before its publication; it has priority over subset (single center) publication during 1 year after study completion; Each Investigator has publication rights after multicenter publication is submitted or 1 year after study completion. Sponsor has the right to comment on the publication and ask for a 90-day delay to protect its intellectual property and/or deletion of any confidential information.
Results Point of Contact
| Name/Title | Anne McClain |
|---|---|
| Organization | Celgene Corporation |
| Phone | 1-888-260-1599 |
| clinicaltrialdisclosure@celgene.com |
- AZA-MDS-001