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A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (HELIOS)

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ClinicalTrials.gov Identifier: NCT01877655
Recruitment Status : Active, not recruiting
First Posted : June 14, 2013
Results First Posted : November 28, 2018
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
Vical
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Cytomegalovirus (CMV)-Positive Recipients
Allogeneic, Hematopoietic Cell Transplant (HCT)
Interventions Biological: ASP0113
Drug: Placebo
Enrollment 514
Recruitment Details A total of 514 participants were enrolled across 11 countries. At least 30% of enrolled participants had cytomegalovirus (CMV) seronegative donor and underwent allogeneic hematopoietic cell transplant (HCT). After the primary study period (day 365) participants were monitored for 5.5 years post-transplant for long-term safety.
Pre-assignment Details Screening assessment occurred from 30 to 5 days before transplant. Participants who met the inclusion and none of the exclusion criteria were randomly assigned in a 1:1 ratio to receive either ASP0113 or placebo. The randomization to treatment was stratified by donor-recipient relatedness and by donor CMV serostatus.
Arm/Group Title Placebo ASP0113 5mg
Hide Arm/Group Description Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0). Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Period Title: Overall Study
Started 263 251
Received Treatment 255 246
Completed 165 154
Not Completed 98 97
Reason Not Completed
Death             57             52
Withdrawal by Subject             18             26
Physician Decision             11             10
Miscellaneous             4             4
Randomized but Never Received Drug             8             5
Arm/Group Title Placebo ASP0113 Total
Hide Arm/Group Description Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0). Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0). Total of all reporting groups
Overall Number of Baseline Participants 263 251 514
Hide Baseline Analysis Population Description
The analysis population was the All Randomized which consisted of all randomized participants whether they received study drug or not.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Year
Number Analyzed 263 participants 251 participants 514 participants
52.0  (13.15) 51.8  (12.41) 51.9  (12.78)
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Female
105
  39.9%
110
  43.8%
215
  41.8%
Male
158
  60.1%
141
  56.2%
299
  58.2%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Hispanic or Latino
11
   4.2%
19
   7.6%
30
   5.8%
Not Hispanic or Latino
252
  95.8%
232
  92.4%
484
  94.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
47
  17.9%
50
  19.9%
97
  18.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   2.3%
7
   2.8%
13
   2.5%
White
189
  71.9%
177
  70.5%
366
  71.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
21
   8.0%
17
   6.8%
38
   7.4%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Strata   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Related Seropositive Donor
65
  24.7%
73
  29.1%
138
  26.8%
Related Seronegative Donor
30
  11.4%
26
  10.4%
56
  10.9%
Non-related Seropositive Donor
96
  36.5%
73
  29.1%
169
  32.9%
Non-related Seronegative Donor
72
  27.4%
79
  31.5%
151
  29.4%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Primary Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Acute Myeloid Leukemia (AML)
126
  47.9%
97
  38.6%
223
  43.4%
Acute Lymphoblastic Leukemia (ALL)
34
  12.9%
34
  13.5%
68
  13.2%
Acute Undifferentiated Leukemia (AUL)
1
   0.4%
2
   0.8%
3
   0.6%
Acute Biphenotypic Leukemia (ABL)
2
   0.8%
2
   0.8%
4
   0.8%
Chronic Myelogenous Leukemia (CML)
6
   2.3%
12
   4.8%
18
   3.5%
Chronic Lymphocytic Leukemia (CLL)
7
   2.7%
10
   4.0%
17
   3.3%
Myelodysplastic Syndrome
46
  17.5%
51
  20.3%
97
  18.9%
Primary or Secondary Myelofibrosis
8
   3.0%
11
   4.4%
19
   3.7%
Lymphoma
33
  12.5%
31
  12.4%
64
  12.5%
Missing
0
   0.0%
1
   0.4%
1
   0.2%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Conditioning Regimen   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Myeloablative
122
  46.4%
120
  47.8%
242
  47.1%
Non-Myeloablative
131
  49.8%
124
  49.4%
255
  49.6%
Missing
10
   3.8%
7
   2.8%
17
   3.3%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Antithymocyte Globulin (ATG) Use   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 251 participants 514 participants
Yes
45
  17.1%
43
  17.1%
88
  17.1%
No
218
  82.9%
208
  82.9%
426
  82.9%
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Centimeteres
Number Analyzed 263 participants 251 participants 514 participants
170.6  (9.91) 169.7  (9.88) 170.2  (9.90)
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 263 participants 251 participants 514 participants
27.0  (5.02) 26.0  (5.05) 26.5  (5.06)
[1]
Measure Analysis Population Description: The analysis population was the all randomized.
1.Primary Outcome
Title Percentage of Participants With Composite of All-Cause Mortality and Adjudicated Cytomegalovirus End Organ Disease (CMV EOD) Through 1 Year Post Transplant
Hide Description This was the composite of all-cause mortality and adjudicated CMV EOD through 1 year posttransplant, The CMV EOD was assessed by the independent and blinded adjudication committee, which counted events that were observed up to day 380 from transplantation. Deaths that occurred up to day 365 from transplant were also counted.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the full analysis set (FAS), which consisted of all randomized participants who received at least one dose of randomized study drug.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Unit of Measure: Percentage of Participants
Participants With Composite Endpoint 30.20 35.37
All-Cause Mortality 28.24 31.71
Adjudicated CMV EOD 3.53 6.10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of all-cause mortality and adjudicated CMV EOD. Analysis was completed using the Cochran-Mantel-Haenszel (CMH) test at the 1-sided 5% level stratified by use of antithymocyte globulin (ATG) and by receipt of a kidney from a living or deceased donor.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.205
Comments P-value based on CMH general association test stratified by donor-recipient relatedness and donor CMV serostatus.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.87 to 1.85
Estimation Comments Odds ratio (ASP0113 vs placebo) and 95% CI was based on CMH general association test stratified by donor-recipient relatedness & donor CMV serostatus.
2.Secondary Outcome
Title Percentage of Participants With Protocol-Defined CMV Viremia Through 1 Year Posttransplant
Hide Description Protocol-defined CMV viremia was defined as a CMV plasma viral load ≥1000 IU/mL as assessed by the central laboratory. Rate was based on cumulative incidence function estimated at 1 year. The central laboratory had the lower limit of quantification [LLOQ] for CMV viral load assessment, so when the viral load was below the LLOQ the actual viral load reading was not possible and was denoted as ≤LLOQ. If participant had any CMV viral load assessments greater than the LLOQ it was classified as viremic.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
58.6
(52.0 to 64.6)
56.7
(50.1 to 62.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of CMV viremia through 1 year posttransplant. CMV viremia was defined by the protocol as CMV plasma viral load ≥ 1000 IU/mL as assessed by the central laboratory. The 95% CI was based on cumulative incidence function CMV viremia rate at 1 year.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.748
Comments P-value based on cox proportional hazards model parameter estimate for the treatment effect.
Method Cox Proportional Hazard Model
Comments Parameter estimate from cox proportional hazard model (ASP0113 v placebo) with treatment & randomization strata adjusted for death as a competing risk
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.76 to 1.22
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Adjudicated CMV-Specific Antiviral Therapy (AVT) Through 1 Year Posttransplant
Hide Description The CMV-specific AVT use was adjudicated by the independent and blinded committee. When the CMV-specific AVT was initiated, a central CMV viral load was obtained weekly until it was discontinued. Participants without any CMV-specific AVT events were censored on the last study evaluation.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
53.2
(46.8 to 59.1)
54.6
(48.1 to 60.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of CMV-specific antiviral therapy (AVT) through 1 year. Time to first adjudicated CMV-specific therapy was defined as time to the start of AVT for CMV viremia. CMV-specific AVT was determined by the adjudication committee. Rate was based on cumulative incidence function estimate at 1 year.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.888
Comments P-value based on cox proportional hazards model parameter estimate for the treatment effect.
Method Cox Proportional Hazard Model
Comments Parameter estimate from cox proportional hazard model (ASP0113 v placebo) with treatment & randomization strata adjusted for death as a competing risk
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.80 to 1.29
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With a Composite Endpoint of Protocol-defined CMV Viremia and Adjudicated CMV-Specific AVT Use
Hide Description Protocol-defined CMV viremia was as CMV plasma viral load ≥ 1000 IU/mL as assessed by the central laboratory. The CMV-specific AVT was determined by the adjudication committee. Participants with no posttransplant viral load data were excluded from the analysis.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Unit of Measure: Percentage of Participants
60.78 60.98
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of composite of CMV viremia and adjudicated CMV-AVT. The CMV viremia was defined by the protocol as CMV plasma viral load ≥ 1000 IU/mL as assessed by the central laboratory. CMV-specific AVT was determined by the adjudication committee. Participants with no posttransplant viral load data were excluded from the analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.802
Comments P value based on CMH general association test stratified by donor-recipient relatedness and donor CMV serostatus.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.73 to 1.51
Estimation Comments Odds ratio (ASP0113 vs placebo) and 95% CI based on CMH general association test stratified by donor recipient relatedness and donor CMV serostatus.
5.Secondary Outcome
Title Percentage of Participants With First Occurrence of Adjudicated CMV-specific AVT or Adjudicated Diagnosis of CMV EOD After Study Drug First Injection Through 1 Year Posttransplant
Hide Description Rate was based on cumulative incidence function estimate at 1 year. Time to first CMV-specific AVT was defined as time to the start of AVT for CMV viremia or CMV EOD. CMV-specific AVT and EOD were determined by the adjudication committee. This endpoint was a composite endpoint based on the independent adjudication committee assessments of CMV-specific AVT and CMV EOD.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
54.4
(48.0 to 60.3)
55.4
(48.9 to 61.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of rate of adjudicated CMV AVT or CMV EOD. Time to first CMV-specific AVT was defined as time to the start of AVT for CMV viremia or CMV EOD. CMV-specific AVT and EOD and were determined by the adjudication committee. Rate based on cumulative incidence function estimate at 1 year.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.928
Comments P value based on cox proportional hazards model parameter estimate for the treatment effect.
Method Cox Proportional Hazards Model
Comments Parameter estimate from cox proportional hazard model (ASP0113 v placebo) with treatment & randomization strata adjusted for death as a competing risk
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.28 to 0.20
Estimation Comments [Not Specified]
6.Secondary Outcome
Title All-Cause Mortality at 1 Year Posttransplant
Hide Description All-cause mortality through 1-year post-transplantation summary included all deaths and unknown survival status. For the known deaths, the adjudication committee assessed results and summarized them according to the following category: Mortality due to the participant’s primary disease, and mortality due to causes unrelated to the participant’s primary disease. Participants with unknown survival status at 1 year were considered dead for this analysis.
Time Frame From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the FAS.
Arm/Group Title Placebo ASP0113
Hide Arm/Group Description:
Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
Overall Number of Participants Analyzed 255 246
Measure Type: Number
Unit of Measure: Percentage of Participants
28.24 31.71
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, ASP0113
Comments Analysis of all-cause mortality at 1 year. Participants with unknown survival status at 1 year were considered dead for this analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments P value based on cox proportional hazards model parameter estimate for the treatment effect.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.81 to 1.73
Estimation Comments Odds ratio (ASP0113 vs placebo) and 95% CI based on CMH general association test stratified by donor-recipient relatedness and donor CMV serostatus.
Time Frame From first dose of study drug up to 30 days after last dose of study drug (Day 365)
Adverse Event Reporting Description Treatment Emergent Adverse Event (TEAE) was defined as an adverse event observed after the first dose of study drug injection through Day 365 and within 30 days of the last dose of study drug. Drug-related TEAE was defined as any TEAE with at least possible relationship to study treatment as assessed by the investigator or with missing assessment of the causal relationship.
 
Arm/Group Title Placebo ASP0113 5mg
Hide Arm/Group Description Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0). Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
All-Cause Mortality
Placebo ASP0113 5mg
Affected / at Risk (%) Affected / at Risk (%)
Total   68/255 (26.67%)      67/246 (27.24%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo ASP0113 5mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   221/255 (86.67%)      221/246 (89.84%)    
Blood and lymphatic system disorders     
Agranulocytosis  1  3/255 (1.18%)  4 0/246 (0.00%)  0
Anaemia  1  1/255 (0.39%)  1 3/246 (1.22%)  4
Aplasia pure red cell  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Bone marrow failure  1  1/255 (0.39%)  1 3/246 (1.22%)  3
Coagulopathy  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Eosinophilia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Febrile bone marrow aplasia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Febrile neutropenia  1  11/255 (4.31%)  13 11/246 (4.47%)  14
Haemolytic anaemia  1  2/255 (0.78%)  2 3/246 (1.22%)  3
Haemolytic uraemic syndrome  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Neutropenia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pancytopenia  1  5/255 (1.96%)  6 5/246 (2.03%)  6
Thrombocytopenia  1  0/255 (0.00%)  0 3/246 (1.22%)  3
Thrombotic microangiopathy  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Cardiac disorders     
Acute myocardial infarction  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Angina pectoris  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Arrhythmia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Atrial fibrillation  1  3/255 (1.18%)  3 4/246 (1.63%)  5
Cardiac failure  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Cardiac failure acute  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cardiac failure congestive  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cardiac tamponade  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cardio-respiratory arrest  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Cardiogenic shock  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pericardial effusion  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Pericarditis  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pulseless electrical activity  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Supraventricular tachycardia  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Ear and labyrinth disorders     
Aural polyp  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Deafness neurosensory  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Eye disorders     
Mydriasis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Abdominal pain  1  2/255 (0.78%)  3 2/246 (0.81%)  2
Abdominal pain lower  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Anal fissure  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Ascites  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Colitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Diarrhoea  1  11/255 (4.31%)  11 10/246 (4.07%)  13
Dysphagia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Enteritis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Enterocolitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Gastritis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Gastrointestinal haemorrhage  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Gastrointestinal toxicity  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Gastrooesophagitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Haematochezia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Impaired gastric emptying  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Intra-abdominal haemorrhage  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Large intestinal haemorrhage  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Megacolon  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Nausea  1  8/255 (3.14%)  8 10/246 (4.07%)  10
Oesophagitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Oral pain  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pancreatitis  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pancreatitis acute  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pneumatosis intestinalis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Proctalgia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Rectal haemorrhage  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Small intestinal perforation  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Vomiting  1  7/255 (2.75%)  7 11/246 (4.47%)  12
General disorders     
Asthenia  1  2/255 (0.78%)  2 4/246 (1.63%)  4
Chest pain  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Chills  1  0/255 (0.00%)  0 3/246 (1.22%)  3
Drug resistance  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Fatigue  1  1/255 (0.39%)  1 2/246 (0.81%)  2
General physical health deterioration  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Infusion site extravasation  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Malaise  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Mucosal inflammation  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Multi-organ failure  1  2/255 (0.78%)  2 6/246 (2.44%)  6
Non-cardiac chest pain  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Oedema due to cardiac disease  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pyrexia  1  23/255 (9.02%)  29 26/246 (10.57%)  27
Serositis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Sudden death  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Systemic inflammatory response syndrome  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Hepatobiliary disorders     
Acute hepatic failure  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cholecystitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Cholecystitis acute  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Hepatic vein occlusion  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Hyperbilirubinaemia  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Venoocclusive liver disease  1  4/255 (1.57%)  4 5/246 (2.03%)  5
Immune system disorders     
Acute graft versus host disease  1  9/255 (3.53%)  10 7/246 (2.85%)  7
Acute graft versus host disease in intestine  1  76/255 (29.80%)  120 76/246 (30.89%)  123
Acute graft versus host disease in liver  1  24/255 (9.41%)  30 18/246 (7.32%)  23
Acute graft versus host disease in skin  1  122/255 (47.84%)  171 118/246 (47.97%)  165
Alloimmunisation  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Chronic graft versus host disease  1  4/255 (1.57%)  5 2/246 (0.81%)  2
Chronic graft versus host disease in intestine  1  6/255 (2.35%)  7 3/246 (1.22%)  3
Chronic graft versus host disease in liver  1  7/255 (2.75%)  7 3/246 (1.22%)  3
Chronic graft versus host disease in skin  1  5/255 (1.96%)  5 1/246 (0.41%)  1
Infections and infestations     
Abdominal abscess  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Abscess intestinal  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Acinetobacter bacteraemia  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Adenovirus infection  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Anorectal cellulitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Appendicitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Aspergillosis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Atypical mycobacterial infection  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Atypical pneumonia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
BK virus infection  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Bacteraemia  1  4/255 (1.57%)  4 4/246 (1.63%)  4
Bacterial infection  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Bacterial sepsis  1  3/255 (1.18%)  4 3/246 (1.22%)  3
Brain abscess  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Bronchitis  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Bronchopneumonia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Bronchopulmonary aspergillosis  1  3/255 (1.18%)  4 4/246 (1.63%)  4
Campylobacter gastroenteritis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Catheter site infection  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cellulitis  1  1/255 (0.39%)  1 3/246 (1.22%)  3
Cerebral aspergillosis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Citrobacter sepsis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Clostridium difficile colitis  1  5/255 (1.96%)  5 2/246 (0.81%)  2
Clostridium difficile infection  1  4/255 (1.57%)  5 3/246 (1.22%)  3
Corona virus infection  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Cystitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Cystitis bacterial  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cytomegalovirus colitis  1  1/255 (0.39%)  1 3/246 (1.22%)  3
Cytomegalovirus gastritis  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Cytomegalovirus gastroenteritis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Cytomegalovirus infection  1  6/255 (2.35%)  6 10/246 (4.07%)  10
Cytomegalovirus viraemia  1  9/255 (3.53%)  11 11/246 (4.47%)  13
Device related infection  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Device related sepsis  1  3/255 (1.18%)  3 0/246 (0.00%)  0
Diarrhoea infectious  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Diverticulitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Encephalitis cytomegalovirus  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Encephalitis herpes  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Encephalitis viral  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Enterococcal bacteraemia  1  2/255 (0.78%)  3 1/246 (0.41%)  1
Enterococcal sepsis  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Enterocolitis bacterial  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Enterocolitis infectious  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Epstein-Barr viraemia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Epstein-Barr virus infection  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Escherichia bacteraemia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Escherichia sepsis  1  1/255 (0.39%)  1 3/246 (1.22%)  4
Escherichia urinary tract infection  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Gangrene  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Gastroenteritis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Gastroenteritis adenovirus  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Genital herpes  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Hepatic candidiasis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Herpes simplex  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Herpes zoster  1  5/255 (1.96%)  7 4/246 (1.63%)  4
Herpes zoster ophthalmic  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Human herpesvirus 6 infection  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Human polyomavirus infection  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Infected skin ulcer  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Infection  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Influenza  1  3/255 (1.18%)  3 3/246 (1.22%)  3
Klebsiella bacteraemia  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Klebsiella sepsis  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Lobar pneumonia  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Localised infection  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Lower respiratory tract infection bacterial  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Lung infection  1  2/255 (0.78%)  3 4/246 (1.63%)  4
Meningitis aseptic  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Neutropenic sepsis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Oesophageal candidiasis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Oral candidiasis  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Oral herpes  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Peritonitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pharyngitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pneumocystis jiroveci pneumonia  1  2/255 (0.78%)  2 2/246 (0.81%)  3
Pneumonia  1  15/255 (5.88%)  18 19/246 (7.72%)  20
Pneumonia adenoviral  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Pneumonia bacterial  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pneumonia cytomegaloviral  1  1/255 (0.39%)  1 3/246 (1.22%)  3
Pneumonia escherichia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pneumonia fungal  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pneumonia herpes viral  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pneumonia influenzal  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pneumonia klebsiella  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pneumonia legionella  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Pneumonia respiratory syncytial viral  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pneumonia staphylococcal  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Pneumonia streptococcal  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pneumonia viral  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Postoperative wound infection  1  0/255 (0.00%)  0 1/246 (0.41%)  2
Pseudomonal bacteraemia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Pulmonary mycosis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Respiratory syncytial virus infection  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Respiratory tract infection  1  3/255 (1.18%)  3 4/246 (1.63%)  5
Sepsis  1  20/255 (7.84%)  23 14/246 (5.69%)  14
Septic shock  1  9/255 (3.53%)  10 10/246 (4.07%)  10
Sialoadenitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Sinusitis  1  3/255 (1.18%)  3 1/246 (0.41%)  1
Sinusitis fungal  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Skin infection  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Staphylococcal bacteraemia  1  4/255 (1.57%)  4 5/246 (2.03%)  6
Staphylococcal sepsis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Streptococcal bacteraemia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Streptococcal sepsis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Subcutaneous abscess  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Systemic mycosis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Tubo-ovarian abscess  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Upper respiratory tract infection  1  1/255 (0.39%)  1 4/246 (1.63%)  4
Urinary tract infection  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Urinary tract infection bacterial  1  2/255 (0.78%)  2 3/246 (1.22%)  3
Urinary tract infection enterococcal  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Urinary tract infection fungal  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Viral haemorrhagic cystitis  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Viral infection  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Injury, poisoning and procedural complications     
Blood stem cell transplant failure  1  4/255 (1.57%)  4 3/246 (1.22%)  3
Drug dose omission  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Facial bones fracture  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Fall  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Muscle strain  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Road traffic accident  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Spinal compression fracture  1  2/255 (0.78%)  2 1/246 (0.41%)  2
Spinal fracture  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Subdural haematoma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Transfusion microchimerism  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Transplant failure  1  3/255 (1.18%)  3 0/246 (0.00%)  0
Investigations     
Blood bilirubin increased  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Computerised tomogram thorax abnormal  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Immunosuppressant drug level increased  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Liver function test abnormal  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Platelet count decreased  1  1/255 (0.39%)  1 1/246 (0.41%)  3
Transaminases increased  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Weight decreased  1  0/255 (0.00%)  0 1/246 (0.41%)  3
Metabolism and nutrition disorders     
Cachexia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Decreased appetite  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Dehydration  1  4/255 (1.57%)  4 4/246 (1.63%)  4
Diabetes mellitus  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Diabetes mellitus inadequate control  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Failure to thrive  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Fluid overload  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Hypercalcaemia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Hyperglycaemia  1  2/255 (0.78%)  2 2/246 (0.81%)  2
Hyperkalaemia  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Hypoalbuminaemia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Hypocalcaemia  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Hyponatraemia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Malnutrition  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Tumour lysis syndrome  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Back pain  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Chondrocalcinosis pyrophosphate  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Intervertebral disc protrusion  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Myopathy  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Polyarthritis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Rhabdomyolysis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia  1  1/255 (0.39%)  3 0/246 (0.00%)  0
Acute lymphocytic leukaemia recurrent  1  6/255 (2.35%)  8 5/246 (2.03%)  5
Acute myeloid leukaemia  1  2/255 (0.78%)  2 6/246 (2.44%)  6
Acute myeloid leukaemia recurrent  1  18/255 (7.06%)  21 17/246 (6.91%)  22
Adult T-cell lymphoma/leukaemia recurrent  1  0/255 (0.00%)  0 1/246 (0.41%)  2
Basal cell carcinoma  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Central nervous system lymphoma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Chloroma  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Chronic lymphocytic leukaemia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Chronic lymphocytic leukaemia recurrent  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Chronic myeloid leukaemia  1  2/255 (0.78%)  2 2/246 (0.81%)  3
Chronic myelomonocytic leukaemia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Diffuse large B-cell lymphoma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Hepatic cancer metastatic  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Hodgkin's disease  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Kaposi's sarcoma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Leukaemia recurrent  1  2/255 (0.78%)  2 3/246 (1.22%)  4
Leukaemic infiltration brain  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Lymphoma  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Malignant melanoma  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Malignant neoplasm progression  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Monoclonal gammopathy  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Mycosis fungoides recurrent  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Myelodysplastic syndrome  1  3/255 (1.18%)  3 5/246 (2.03%)  5
Myelofibrosis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Non-Hodgkin's lymphoma recurrent  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Peripheral T-cell lymphoma unspecified recurrent  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Post transplant lymphoproliferative disorder  1  3/255 (1.18%)  3 2/246 (0.81%)  2
Small cell lung cancer  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Squamous cell carcinoma  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Squamous cell carcinoma of skin  1  0/255 (0.00%)  0 1/246 (0.41%)  1
T-cell lymphoma  1  0/255 (0.00%)  0 1/246 (0.41%)  1
T-cell lymphoma recurrent  1  1/255 (0.39%)  1 0/246 (0.00%)  0
T-cell type acute leukaemia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Nervous system disorders     
Acute polyneuropathy  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Amnesia  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Brain oedema  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Central nervous system lesion  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Cerebrovascular accident  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Coma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Convulsion  1  2/255 (0.78%)  2 3/246 (1.22%)  3
Dizziness  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Encephalitis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Encephalopathy  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Facial paresis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Headache  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Memory impairment  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Migraine  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Neurological decompensation  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Paraplegia  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Syncope  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Thalamus haemorrhage  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Transient ischaemic attack  1  0/255 (0.00%)  0 2/246 (0.81%)  2
VIIth nerve paralysis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Psychiatric disorders     
Confusional state  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Delirium  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Disorientation  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Mania  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Mental disorder  1  1/255 (0.39%)  2 1/246 (0.41%)  1
Mental status changes  1  2/255 (0.78%)  2 3/246 (1.22%)  3
Suicidal ideation  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Renal and urinary disorders     
Haematuria  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Renal colic  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Renal failure  1  5/255 (1.96%)  6 3/246 (1.22%)  3
Renal failure acute  1  41/255 (16.08%)  46 28/246 (11.38%)  38
Renal failure chronic  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Renal impairment  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Renal injury  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Renal tubular necrosis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Urinary tract obstruction  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Acute respiratory distress syndrome  1  6/255 (2.35%)  6 0/246 (0.00%)  0
Acute respiratory failure  1  4/255 (1.57%)  4 2/246 (0.81%)  2
Atelectasis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Cough  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Dyspnoea  1  4/255 (1.57%)  4 3/246 (1.22%)  4
Dyspnoea exertional  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Epistaxis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Haemoptysis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Hypoxia  1  2/255 (0.78%)  2 3/246 (1.22%)  3
Idiopathic pneumonia syndrome  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Interstitial lung disease  1  1/255 (0.39%)  2 3/246 (1.22%)  3
Mediastinal mass  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Obliterative bronchiolitis  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Obstructive airways disorder  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Organising pneumonia  1  0/255 (0.00%)  0 2/246 (0.81%)  2
Pleural effusion  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pneumonitis  1  7/255 (2.75%)  7 1/246 (0.41%)  1
Pulmonary alveolar haemorrhage  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pulmonary embolism  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Pulmonary haemorrhage  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Pulmonary oedema  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Pulmonary thrombosis  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Respiratory arrest  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Respiratory distress  1  2/255 (0.78%)  2 1/246 (0.41%)  1
Respiratory failure  1  11/255 (4.31%)  13 8/246 (3.25%)  8
Wheezing  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Skin and subcutaneous tissue disorders     
Diabetic foot  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Pain of skin  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Rash  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Rash maculo-papular  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Skin lesion  1  0/255 (0.00%)  0 1/246 (0.41%)  2
Stasis dermatitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Toxic epidermal necrolysis  1  1/255 (0.39%)  1 1/246 (0.41%)  3
Urticaria  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Surgical and medical procedures     
Appendicectomy  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Central venous catheter removal  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Colectomy  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Donor leukocyte infusion  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Drug therapy  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Stem cell transplant  1  1/255 (0.39%)  1 2/246 (0.81%)  2
Transurethral prostatectomy  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Vascular disorders     
Deep vein thrombosis  1  2/255 (0.78%)  2 0/246 (0.00%)  0
Haematoma  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Hypotension  1  3/255 (1.18%)  3 2/246 (0.81%)  2
Microangiopathy  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Orthostatic hypotension  1  0/255 (0.00%)  0 1/246 (0.41%)  1
Thrombophlebitis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
Venoocclusive disease  1  1/255 (0.39%)  1 1/246 (0.41%)  1
Venous thrombosis  1  1/255 (0.39%)  1 0/246 (0.00%)  0
1
Term from vocabulary, MedDRA 16
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo ASP0113 5mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   254/255 (99.61%)      244/246 (99.19%)    
Blood and lymphatic system disorders     
Anaemia  1  75/255 (29.41%)  160 66/246 (26.83%)  146
Febrile neutropenia  1  92/255 (36.08%)  98 91/246 (36.99%)  101
Leukopenia  1  23/255 (9.02%)  56 20/246 (8.13%)  51
Neutropenia  1  65/255 (25.49%)  98 65/246 (26.42%)  99
Pancytopenia  1  18/255 (7.06%)  19 21/246 (8.54%)  21
Thrombocytopenia  1  48/255 (18.82%)  111 49/246 (19.92%)  131
Cardiac disorders     
Tachycardia  1  22/255 (8.63%)  24 22/246 (8.94%)  28
Eye disorders     
Conjunctivitis  1  17/255 (6.67%)  18 12/246 (4.88%)  12
Dry eye  1  37/255 (14.51%)  39 42/246 (17.07%)  45
Gastrointestinal disorders     
Abdominal discomfort  1  8/255 (3.14%)  11 13/246 (5.28%)  15
Abdominal distension  1  22/255 (8.63%)  22 15/246 (6.10%)  18
Abdominal pain  1  60/255 (23.53%)  83 62/246 (25.20%)  84
Abdominal pain upper  1  33/255 (12.94%)  37 26/246 (10.57%)  32
Constipation  1  103/255 (40.39%)  128 90/246 (36.59%)  119
Diarrhoea  1  167/255 (65.49%)  244 166/246 (67.48%)  242
Dry mouth  1  25/255 (9.80%)  31 30/246 (12.20%)  35
Dyspepsia  1  25/255 (9.80%)  27 31/246 (12.60%)  35
Gastritis  1  19/255 (7.45%)  19 19/246 (7.72%)  20
Gastrooesophageal reflux disease  1  16/255 (6.27%)  17 24/246 (9.76%)  25
Haemorrhoids  1  23/255 (9.02%)  26 27/246 (10.98%)  28
Nausea  1  177/255 (69.41%)  261 178/246 (72.36%)  273
Oral pain  1  16/255 (6.27%)  17 19/246 (7.72%)  20
Proctalgia  1  20/255 (7.84%)  20 20/246 (8.13%)  23
Stomatitis  1  69/255 (27.06%)  96 79/246 (32.11%)  105
Vomiting  1  122/255 (47.84%)  178 125/246 (50.81%)  195
General disorders     
Asthenia  1  34/255 (13.33%)  43 30/246 (12.20%)  39
Catheter site pain  1  21/255 (8.24%)  23 22/246 (8.94%)  29
Chills  1  44/255 (17.25%)  59 36/246 (14.63%)  46
Fatigue  1  69/255 (27.06%)  80 58/246 (23.58%)  65
Injection site erythema  1  5/255 (1.96%)  5 49/246 (19.92%)  72
Injection site induration  1  3/255 (1.18%)  3 38/246 (15.45%)  57
Injection site pain  1  47/255 (18.43%)  83 193/246 (78.46%)  1053
Injection site swelling  1  4/255 (1.57%)  4 24/246 (9.76%)  36
Malaise  1  10/255 (3.92%)  11 15/246 (6.10%)  15
Mucosal inflammation  1  101/255 (39.61%)  147 75/246 (30.49%)  94
Oedema  1  21/255 (8.24%)  24 35/246 (14.23%)  39
Oedema peripheral  1  69/255 (27.06%)  95 66/246 (26.83%)  88
Pain  1  32/255 (12.55%)  34 27/246 (10.98%)  34
Pyrexia  1  128/255 (50.20%)  195 123/246 (50.00%)  180
Hepatobiliary disorders     
Hyperbilirubinaemia  1  16/255 (6.27%)  23 13/246 (5.28%)  17
Immune system disorders     
Chronic graft versus host disease  1  60/255 (23.53%)  109 62/246 (25.20%)  110
Chronic graft versus host disease in intestine  1  21/255 (8.24%)  28 20/246 (8.13%)  22
Chronic graft versus host disease in liver  1  35/255 (13.73%)  45 30/246 (12.20%)  43
Chronic graft versus host disease in skin  1  46/255 (18.04%)  51 37/246 (15.04%)  40
Engraftment syndrome  1  9/255 (3.53%)  9 13/246 (5.28%)  15
Hypogammaglobulinaemia  1  19/255 (7.45%)  20 20/246 (8.13%)  20
Infections and infestations     
BK virus infection  1  13/255 (5.10%)  13 13/246 (5.28%)  15
Clostridium difficile infection  1  16/255 (6.27%)  16 17/246 (6.91%)  18
Cytomegalovirus infection  1  51/255 (20.00%)  64 45/246 (18.29%)  68
Cytomegalovirus viraemia  1  96/255 (37.65%)  141 87/246 (35.37%)  132
Device related infection  1  16/255 (6.27%)  16 16/246 (6.50%)  18
Epstein-Barr virus infection  1  13/255 (5.10%)  15 15/246 (6.10%)  16
Escherichia urinary tract infection  1  11/255 (4.31%)  11 13/246 (5.28%)  20
Folliculitis  1  14/255 (5.49%)  18 8/246 (3.25%)  8
Nasopharyngitis  1  12/255 (4.71%)  14 15/246 (6.10%)  15
Oral candidiasis  1  27/255 (10.59%)  31 17/246 (6.91%)  18
Oral herpes  1  17/255 (6.67%)  18 8/246 (3.25%)  13
Pneumonia  1  13/255 (5.10%)  13 13/246 (5.28%)  13
Staphylococcal bacteraemia  1  17/255 (6.67%)  20 20/246 (8.13%)  23
Upper respiratory tract infection  1  27/255 (10.59%)  36 22/246 (8.94%)  24
Injury, poisoning and procedural complications     
Fall  1  10/255 (3.92%)  12 15/246 (6.10%)  17
Investigations     
Alanine aminotransferase increased  1  31/255 (12.16%)  47 33/246 (13.41%)  66
Aspartate aminotransferase increased  1  30/255 (11.76%)  45 30/246 (12.20%)  49
Blood alkaline phosphatase increased  1  17/255 (6.67%)  24 18/246 (7.32%)  23
Blood bilirubin increased  1  23/255 (9.02%)  48 21/246 (8.54%)  43
Blood creatinine increased  1  29/255 (11.37%)  42 22/246 (8.94%)  27
Gamma-glutamyltransferase increased  1  13/255 (5.10%)  24 15/246 (6.10%)  26
Neutrophil count decreased  1  33/255 (12.94%)  70 28/246 (11.38%)  62
Platelet count decreased  1  37/255 (14.51%)  83 28/246 (11.38%)  49
Transaminases increased  1  10/255 (3.92%)  11 18/246 (7.32%)  19
Weight decreased  1  15/255 (5.88%)  15 12/246 (4.88%)  15
White blood cell count decreased  1  23/255 (9.02%)  65 24/246 (9.76%)  45
Metabolism and nutrition disorders     
Decreased appetite  1  91/255 (35.69%)  109 72/246 (29.27%)  89
Dehydration  1  13/255 (5.10%)  16 13/246 (5.28%)  31
Diabetes mellitus  1  8/255 (3.14%)  8 17/246 (6.91%)  19
Fluid overload  1  14/255 (5.49%)  14 11/246 (4.47%)  16
Hyperglycaemia  1  66/255 (25.88%)  90 54/246 (21.95%)  81
Hyperkalaemia  1  23/255 (9.02%)  40 30/246 (12.20%)  43
Hyperuricaemia  1  10/255 (3.92%)  14 15/246 (6.10%)  17
Hypoalbuminaemia  1  30/255 (11.76%)  43 24/246 (9.76%)  53
Hypocalcaemia  1  37/255 (14.51%)  58 28/246 (11.38%)  51
Hypokalaemia  1  83/255 (32.55%)  120 92/246 (37.40%)  140
Hypomagnesaemia  1  113/255 (44.31%)  157 113/246 (45.93%)  168
Hyponatraemia  1  25/255 (9.80%)  42 26/246 (10.57%)  32
Hypophosphataemia  1  27/255 (10.59%)  30 24/246 (9.76%)  28
Musculoskeletal and connective tissue disorders     
Arthralgia  1  27/255 (10.59%)  30 30/246 (12.20%)  42
Back pain  1  39/255 (15.29%)  39 44/246 (17.89%)  52
Bone pain  1  13/255 (5.10%)  14 10/246 (4.07%)  12
Muscle spasms  1  19/255 (7.45%)  25 14/246 (5.69%)  15
Muscular weakness  1  14/255 (5.49%)  15 10/246 (4.07%)  10
Musculoskeletal pain  1  14/255 (5.49%)  14 19/246 (7.72%)  21
Myalgia  1  19/255 (7.45%)  22 19/246 (7.72%)  23
Neck pain  1  10/255 (3.92%)  10 16/246 (6.50%)  18
Pain in extremity  1  30/255 (11.76%)  31 32/246 (13.01%)  37
Nervous system disorders     
Dizziness  1  33/255 (12.94%)  38 33/246 (13.41%)  44
Dysgeusia  1  22/255 (8.63%)  22 23/246 (9.35%)  24
Headache  1  103/255 (40.39%)  153 103/246 (41.87%)  150
Neuropathy peripheral  1  17/255 (6.67%)  17 14/246 (5.69%)  17
Tremor  1  46/255 (18.04%)  49 23/246 (9.35%)  24
Psychiatric disorders     
Anxiety  1  44/255 (17.25%)  53 40/246 (16.26%)  42
Depression  1  18/255 (7.06%)  18 11/246 (4.47%)  11
Insomnia  1  76/255 (29.80%)  85 72/246 (29.27%)  86
Renal and urinary disorders     
Dysuria  1  29/255 (11.37%)  33 20/246 (8.13%)  25
Haematuria  1  15/255 (5.88%)  15 7/246 (2.85%)  8
Pollakiuria  1  14/255 (5.49%)  16 8/246 (3.25%)  9
Renal failure  1  16/255 (6.27%)  17 17/246 (6.91%)  19
Respiratory, thoracic and mediastinal disorders     
Cough  1  60/255 (23.53%)  71 55/246 (22.36%)  71
Dyspnoea  1  44/255 (17.25%)  53 40/246 (16.26%)  50
Epistaxis  1  23/255 (9.02%)  28 34/246 (13.82%)  37
Hiccups  1  20/255 (7.84%)  21 22/246 (8.94%)  24
Hypoxia  1  10/255 (3.92%)  12 17/246 (6.91%)  21
Nasal congestion  1  18/255 (7.06%)  20 8/246 (3.25%)  8
Oropharyngeal pain  1  41/255 (16.08%)  42 30/246 (12.20%)  33
Rhinorrhoea  1  16/255 (6.27%)  17 18/246 (7.32%)  19
Skin and subcutaneous tissue disorders     
Drug eruption  1  30/255 (11.76%)  32 29/246 (11.79%)  31
Dry skin  1  20/255 (7.84%)  20 25/246 (10.16%)  26
Erythema  1  28/255 (10.98%)  37 34/246 (13.82%)  50
Pruritus  1  67/255 (26.27%)  85 59/246 (23.98%)  67
Rash  1  52/255 (20.39%)  61 51/246 (20.73%)  67
Rash maculo-papular  1  13/255 (5.10%)  17 12/246 (4.88%)  15
Vascular disorders     
Hypertension  1  83/255 (32.55%)  96 66/246 (26.83%)  78
Hypotension  1  36/255 (14.12%)  37 39/246 (15.85%)  50
1
Term from vocabulary, MedDRA 16
Indicates events were collected by systematic assessment
In Oct 2014 data monitoring committee informed Astellas of the results of the first futility analysis. The FDA considered data for 68 participants included in futility analysis compromised and asked that it is not included in final efficacy analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
Name/Title: Clinical Trial Disclosure
Organization: Astellas Pharma Global Development, Inc.
Phone: 800-888-7704 ext 5473
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01877655     History of Changes
Other Study ID Numbers: 0113-CL-1004
2013-000903-18 ( EudraCT Number )
First Submitted: June 12, 2013
First Posted: June 14, 2013
Results First Submitted: September 17, 2018
Results First Posted: November 28, 2018
Last Update Posted: March 6, 2019