Study of US-ATG-F to Prevent Chronic Graft Versus Host Disease (GVHD)

• Sponsor: Neovii Biotech (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01295710
• Collaborator: (none)
• Enrollment: 260
• Locations: 28
• Arms: 2
• Actual Duration (Months): 48.2
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study objective is to compare the efficacy and safety of US-ATG-F as a supplement to standard of care prophylaxis versus standard of care prophylaxis alone in moderate to severe chronic GVHD-free survival.

Condition or Disease	Intervention/Treatment	Phase
GVHD; Adult Acute Myeloid Leukemia; Adult Acute Lymphoid Leukemia; Myelodysplastic Syndrome	Biological: US-ATG-F; Biological: Placebo	Phase 3

Detailed Description

This study is randomized, prospective, double-blind, placebo-controlled, phase 3 study evaluating the prevention of moderate to severe chronic GVHD in patients undergoing bone marrow or peripheral blood stem cell transplantation from matched, unrelated donors for acute leukemia and myelodysplastic syndrome during the first year after transplant.

Patients meeting all the inclusion and none of the exclusion criteria will be randomized (1:1). All patients will receive premedication and study drug 3 days prior to transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase 3 Study of US-ATG-F to Prevent Moderate to Severe Chronic GVHD in Adult Acute Myeloid Leukemia, Acute Lymphoid Leukemia, and Myelodysplastic Syndrome Patients After Allogeneic Stem Cell Transplantation From Unrelated Donors
• Actual Study Start Date: Oct 10, 2011
• Actual Primary Completion Date: Oct 15, 2015
• Actual Study Completion Date: Oct 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: US-ATG-F 20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	Biological: US-ATG-F; 20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation; Other Names: Anti-human-T-lymphocyte Immune Globulin, Rabbit
Placebo Comparator: Placebo 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	Biological: Placebo; 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation

Outcome Measures

Primary Outcome Measures

1. Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD According to 2005 NIH Criteria as Determined by the Independent Endpoint Committee or Death From Any Cause After Allogeneic Stem Cell Transplantation [Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, or death from any cause, assessed up to 48 months]

   Participants with first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee or death from any cause after allogeneic stem cell transplantation, with a target of 124 total events of moderate or severe chronic GVHD, or death from any cause

Secondary Outcome Measures

1. Overall Survival [Time from first study drug administration until the occurrence of death from any cause, assessed up to 48 months]

   Incidence of death from any cause

2. Number of Participants With Chronic GVHD Mild to Severe [Time from first study drug administration until the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks

3. Number of Participants With Chronic GVHD Moderate to Severe [Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks

4. Number of Participants With Chronic GVHD Severe [Time from first study drug administration until the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks

5. Number of Participants With Acute GVHD Grade I-IV [Time from first study drug administration until the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks

6. Number of Participants With Acute GVHD Grade II-IV [Time from first study drug administration until the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks

7. Number of Participants With Acute GVHD Grade III-IV [Time from first study drug administration until the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months]

   Participants with the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks

8. Number of Participants With Relapse [Time from first study drug administration until the occurrence of relapse, with death as competing risk, assessed up to 48 months]

   Participants with relapse or disease recurrence, with death as competing risk

9. Disease-free Survival [Time from first study drug administration until the occurrence of relapse or death, assessed up to 48 months]

   Incidence of relapse or death

10. Number of Participants With Transplant Related Mortality [Time from first study drug administration until the occurrence of transplant related mortality, assessed up to 48 months]

    Participants with transplant related mortality

11. Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD [Time from first study drug administration until start of systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks, assessed up to 48 months]

    Participants who started on systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Patients designated to undergo allogeneic peripheral blood or bone marrow stem cell transplantation following the diagnosis of one of the primary diseases in early or intermediate disease status (i.e., acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome)

• Patients with an unrelated HLA-A,-B, -C and -DRBI matched donor

• Patients with a Karnofsky Performance Score ≥ 70%

Key Exclusion Criteria:

• Clinically significant concomitant diseases (i.e., cardiac, pulmonary, renal and CNS)

• Bacterial, viral, or fungal infections

• Known positive for Hepatitis B surfaces antigen, or Hepatitis C antibody, or who have been tested positive for HIV

• Patients with any concurrent malignancy. Cancer treated with curative intent < 5 years previously will not be allowed except for patients with resected basal cell carcinoma or treated cervical carcinoma in situ

• Known contraindications to the administration of rabbit immunoglobulin antibodies

• Hypersensitivity to methylprednisolone, tacrolimus, methotrexate or any excipients contains in these products

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91019
2	Stanford University Medical Center, BMT	Stanford	California	United States	94305
3	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	University of Chicago Medical Center	Chicago	Illinois	United States	60637
6	Loyola University Medical Center	Maywood	Illinois	United States	60153
7	University of Kansas Medical Center	Westwood	Kansas	United States	66205
8	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02215
12	Mayo Clinic	Rochester	Minnesota	United States	55905
13	Washington University Medical Center	Saint Louis	Missouri	United States	63110
14	Weill Cornell Medical Center	New York	New York	United States	10065
15	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27599
16	Duke University Medical Center	Durham	North Carolina	United States	27710
17	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
18	Oregon Health and Science University	Portland	Oregon	United States	97239
19	Penn State Hershey Cancer Institute	Hershey	Pennsylvania	United States	17033
20	Abramson Cancer Center of the University at Perlman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
21	Vanderbilt University Medical Center, Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37232
22	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
23	Texas Transplant Physician's Group	San Antonio	Texas	United States	78229
24	University of Utah School of Medicine	Salt Lake City	Utah	United States	84132
25	VA Puget Sound Healthcare System	Seattle	Washington	United States	98108
26	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
27	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
28	Royal Melbourne Hospital	Parkville	Victoria	Australia	03050

Sponsors and Collaborators

• Neovii Biotech

Investigators

• Study Director: Anne Kuan, Neovii Biotech

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Neovii Biotech
• ClinicalTrials.gov Identifier: NCT01295710
• Other Study ID Numbers: IV-ATG-SCT-01
• First Posted: Feb 14, 2011
• Last Update Posted: Apr 9, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Neovii Biotech: adult acute myeloid leukemia; adult acute lymphoid leukemia; adult myelodysplastic syndrome; allogenic stem cell transplantation; unrelated donor; GVHD; US-ATG-F (Anti-human-T-lymphocyte Immune Globulin, Rabbit)
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Syndrome; Immunoglobulins; Antilymphocyte Serum

Study Results

Participant Flow

Pre-assignment Detail	The Enrollment number of 260 participants in the Protocol Section represents the number of patients who were randomized. The number of 254 participants who Started in the Participant Flow module represents the number of patients who were randomized and were treated.

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Period Title: Overall Study
STARTED	126	128
COMPLETED	48	78
NOT COMPLETED	78	50

Baseline Characteristics

Arm/Group Title	US-ATG-F	Placebo	Total
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	Total of all reporting groups
Overall Participants	126	128	254
Age, Customized (Count of Participants)
18 years to ≤40 years	42 33.3%	43 33.6%	85 33.5%
>40 years to 65 years	84 66.7%	85 66.4%	169 66.5%
Sex: Female, Male (Count of Participants)
Female	66 52.4%	49 38.3%	115 45.3%
Male	60 47.6%	79 61.7%	139 54.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 4%	6 4.7%	11 4.3%
Not Hispanic or Latino	119 94.4%	117 91.4%	236 92.9%
Unknown or Not Reported	2 1.6%	5 3.9%	7 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.8%	1 0.4%
Asian	2 1.6%	1 0.8%	3 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	4 3.1%	4 1.6%
White	117 92.9%	117 91.4%	234 92.1%
More than one race	0 0%	1 0.8%	1 0.4%
Unknown or Not Reported	7 5.6%	4 3.1%	11 4.3%
Region of Enrollment (Count of Participants)
United States	124 98.4%	125 97.7%	249 98%
Australia	2 1.6%	3 2.3%	5 2%
Disease (Count of Participants)
Acute lymphoid leukemia (ALL)	23 18.3%	34 26.6%	57 22.4%
Myelodysplastic syndrome (MDS)	19 15.1%	14 10.9%	33 13%
Acute myeloid leukemia (AML)	83 65.9%	80 62.5%	163 64.2%
Biphenotypic AML/ALL	1 0.8%	0 0%	1 0.4%
Source of stem cells (Count of Participants)
Bone marrow	22 17.5%	27 21.1%	49 19.3%
Peripheral blood	95 75.4%	101 78.9%	196 77.2%
No stem cell transplantation	9 7.1%	0 0%	9 3.5%
Conditioning regimen (Count of Participants)
Cyclophosphamide & total body irradiation (CY-TBI)	31 24.6%	37 28.9%	68 26.8%
Busulfan & cyclophosphamide (BU-CY)	47 37.3%	37 28.9%	84 33.1%
Fludarabine & busulfan (FLU-BU)	48 38.1%	54 42.2%	102 40.2%
ALC at Study Day -3 Overall Study (Count of Participants)
ALC ≤ 0.1 x 10^9 lymphocytes/L	51 40.5%	41 32%	92 36.2%
ALC > 0.1 x 10^9 lymphocytes/L	64 50.8%	74 57.8%	138 54.3%
Not tested	11 8.7%	13 10.2%	24 9.4%
ALC at Study Day -3 by Conditioning Regimen (Count of Participants)
ALC ≤ 0.1 x 10^9 lymphocytes/L	22 17.5%	24 18.8%	46 18.1%
ALC > 0.1 x 10^9 lymphocytes/L	7 5.6%	11 8.6%	18 7.1%
Not tested	2 1.6%	2 1.6%	4 1.6%
ALC ≤ 0.1 x 10^9 lymphocytes/L	6 4.8%	2 1.6%	8 3.1%
ALC > 0.1 x 10^9 lymphocytes/L	39 31%	31 24.2%	70 27.6%
Not tested	2 1.6%	4 3.1%	6 2.4%
ALC ≤ 0.1 x 10^9 lymphocytes/L	23 18.3%	15 11.7%	38 15%
ALC > 0.1 x 10^9 lymphocytes/L	18 14.3%	32 25%	50 19.7%
Not tested	7 5.6%	7 5.5%	14 5.5%
ALC ≤ 0.1 x 10^9 lymphocytes/L	29 23%	17 13.3%	46 18.1%
ALC > 0.1 x 10^9 lymphocytes/L	57 45.2%	63 49.2%	120 47.2%
Not tested	9 7.1%	11 8.6%	20 7.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD According to 2005 NIH Criteria as Determined by the Independent Endpoint Committee or Death From Any Cause After Allogeneic Stem Cell Transplantation
Description	Participants with first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee or death from any cause after allogeneic stem cell transplantation, with a target of 124 total events of moderate or severe chronic GVHD, or death from any cause
Time Frame	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, or death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	60 47.6%	72 56.3%

2. Secondary Outcome

Title	Overall Survival
Description	Incidence of death from any cause
Time Frame	Time from first study drug administration until the occurrence of death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	49 38.9%	36 28.1%

3. Secondary Outcome

Title	Number of Participants With Chronic GVHD Mild to Severe
Description	Participants with the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	18 14.3%	50 39.1%

4. Secondary Outcome

Title	Number of Participants With Chronic GVHD Moderate to Severe
Description	Participants with the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	13 10.3%	45 35.2%

5. Secondary Outcome

Title	Number of Participants With Chronic GVHD Severe
Description	Participants with the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	3 2.4%	16 12.5%

6. Secondary Outcome

Title	Number of Participants With Acute GVHD Grade I-IV
Description	Participants with the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	48 38.1%	71 55.5%

7. Secondary Outcome

Title	Number of Participants With Acute GVHD Grade II-IV
Description	Participants with the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	28 22.2%	53 41.4%

8. Secondary Outcome

Title	Number of Participants With Acute GVHD Grade III-IV
Description	Participants with the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	8 6.3%	17 13.3%

9. Secondary Outcome

Title	Number of Participants With Relapse
Description	Participants with relapse or disease recurrence, with death as competing risk
Time Frame	Time from first study drug administration until the occurrence of relapse, with death as competing risk, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	37 29.4%	26 20.3%

10. Secondary Outcome

Title	Disease-free Survival
Description	Incidence of relapse or death
Time Frame	Time from first study drug administration until the occurrence of relapse or death, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	61 48.4%	49 38.3%

11. Secondary Outcome

Title	Number of Participants With Transplant Related Mortality
Description	Participants with transplant related mortality
Time Frame	Time from first study drug administration until the occurrence of transplant related mortality, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	24 19%	23 18%

12. Secondary Outcome

Title	Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD
Description	Participants who started on systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks
Time Frame	Time from first study drug administration until start of systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	8 6.3%	33 25.8%

13. Post-Hoc Outcome

Title	Number of Participants With First Occurrence of Moderate or Severe Chronic GVHD According to 2005 NIH Criteria as Determined by Principal Investigator or Death From Any Cause After Allogeneic Stem Cell Transplantation
Description	Participants with first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators or death from any cause after allogeneic stem cell transplantation, with a target of 124 total events of moderate or severe chronic GVHD or death
Time Frame	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators or death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	63 50%	86 67.2%

14. Post-Hoc Outcome

Title	Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS)
Description	Participants with moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause
Time Frame	Time from first study drug administration until the occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	70 55.6%	81 63.3%

15. Post-Hoc Outcome

Title	Grade III-IV Acute GVHD-free, GRFS
Description	Participants with grade III-IV acute GVHD as determined by the Investigator, moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause
Time Frame	Time from first study drug administration until the occurrence of grade III-IV acute GVHD, moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Count of Participants [Participants]	72 57.1%	85 66.4%

16. Post-Hoc Outcome

Title	Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen
Description	Participants with first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee or death from any cause after allogeneic stem cell transplantation, with a target of 124 total events of moderate or severe chronic GVHD, or death from any cause. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, or death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	20 15.9%	16 12.5%
Regimen: BU-CY	18 14.3%	21 16.4%
Regimen: FLU-BU	22 17.5%	35 27.3%
Regimens: BU-CY + FLU-BU	40 31.7%	56 43.8%

17. Post-Hoc Outcome

Title	Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen
Description	Participants with moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	23 18.3%	20 15.6%
Regimen: BU-CY	21 16.7%	22 17.2%
Regimen: FLU-BU	26 20.6%	39 30.5%
Regimens: BU-CY + FLU-BU	47 37.3%	61 47.7%

18. Post-Hoc Outcome

Title	Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen
Description	Participants with grade III-IV acute GVHD as determined by the Investigator, moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death from any cause. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of grade III-IV acute GVHD, moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, relapse or death, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	23 18.3%	21 16.4%
Regimen: BU-CY	23 18.3%	22 17.2%
Regimen: FLU-BU	26 20.6%	42 32.8%
Regimens: BU-CY + FLU-BU	49 38.9%	64 50%

19. Post-Hoc Outcome

Title	Overall Survival by Conditioning Regimen
Description	Incidence of death from any cause. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of death from any cause, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	17 13.5%	8 6.3%
Regimen: BU-CY	12 9.5%	8 6.3%
Regimen: FLU-BU	20 15.9%	20 15.6%
Regimens: BU-CY + FLU-BU	32 25.4%	28 21.9%

20. Post-Hoc Outcome

Title	Chronic GVHD Mild to Severe by Conditioning Regimen
Description	Participants with the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	7 5.6%	16 12.5%
Regimen: BU-CY	6 4.8%	14 10.9%
Regimen: FLU-BU	5 4%	20 15.6%
Regimens: BU-CY + FLU-BU	11 8.7%	34 26.6%

21. Post-Hoc Outcome

Title	Chronic GVHD Moderate to Severe by Conditioning Regimen
Description	Participants with the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	5 4%	13 10.2%
Regimen: BU-CY	6 4.8%	13 10.2%
Regimen: FLU-BU	2 1.6%	19 14.8%
Regimens: BU-CY + FLU-BU	8 6.3%	32 25%

22. Post-Hoc Outcome

Title	Chronic GVHD Severe by Conditioning Regimen
Description	Participants with the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	1 0.8%	5 3.9%
Regimen: BU-CY	1 0.8%	4 3.1%
Regimen: FLU-BU	1 0.8%	7 5.5%
Regimens: BU-CY + FLU-BU	2 1.6%	11 8.6%

23. Post-Hoc Outcome

Title	Acute GVHD Grade I-IV by Conditioning Regimen
Description	Participants with the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade I-IV, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	13 10.3%	18 14.1%
Regimen: BU-CY	19 15.1%	23 18%
Regimen: FLU-BU	16 12.7%	30 23.4%
Regimens: BU-CY + FLU-BU	35 27.8%	53 41.4%

24. Post-Hoc Outcome

Title	Acute GVHD Grade II-IV by Conditioning Regimen
Description	Participants with the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade II-IV, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	8 6.3%	14 10.9%
Regimen: BU-CY	12 9.5%	17 13.3%
Regimen: FLU-BU	8 6.3%	22 17.2%
Regimens: BU-CY + FLU-BU	20 15.9%	39 30.5%

25. Post-Hoc Outcome

Title	Acute GVHD Grade III-IV by Conditioning Regimen
Description	Participants with the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the first occurrence of acute GVHD grade III-IV, with death and re transplantation as competing risks, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	3 2.4%	2 1.6%
Regimen: BU-CY	4 3.2%	5 3.9%
Regimen: FLU-BU	1 0.8%	10 7.8%
Regimens: BU-CY + FLU-BU	5 4%	15 11.7%

26. Post-Hoc Outcome

Title	Relapse by Conditioning Regimen
Description	Participants with relapse or disease recurrence, with death as competing risk. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of relapse with death as competing risk, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	11 8.7%	6 4.7%
Regimen: BU-CY	8 6.3%	7 5.5%
Regimen: FLU-BU	18 14.3%	13 10.2%
Regimens: BU-CY + FLU-BU	26 20.6%	20 15.6%

27. Post-Hoc Outcome

Title	Disease-free Survival by Conditioning Regimen
Description	Incidence of relapse or death. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of relapse or death, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	21 16.7%	13 10.2%
Regimen: BU-CY	15 11.9%	11 8.6%
Regimen: FLU-BU	25 19.8%	25 19.5%
Regimens: BU-CY + FLU-BU	40 31.7%	36 28.1%

28. Post-Hoc Outcome

Title	Transplant-related Mortality by Conditioning Regimen
Description	Participants with transplant related mortality. Analysis was conducted by conditioning regimen.
Time Frame	Time from first study drug administration until the occurrence of transplant related mortality, assessed up to 48 months

Outcome Measure Data

Analysis Population Description

Analysis of patients who received a specific conditioning regimen

Arm/Group Title	US-ATG-F	Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Measure Participants	126	128
Regimen: CY-TBI	10 7.9%	7 5.5%
Regimen: BU-CY	7 5.6%	4 3.1%
Regimen: FLU-BU	7 5.6%	12 9.4%
Regimens: BU-CY + FLU-BU	14 11.1%	16 12.5%

Adverse Events

Arm/Group Title	US-ATG-F		Placebo
Arm/Group Description	20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation		250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
All Cause Mortality
	US-ATG-F		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	US-ATG-F		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/126 (77.8%)		90/128 (70.3%)
Blood and lymphatic system disorders
Anaemia	2/126 (1.6%)	2	0/128 (0%)	0
Anaemia haemolytic autoimmune	1/126 (0.8%)	1	0/128 (0%)	0
Aplasia pure red cell	0/126 (0%)	0	1/128 (0.8%)	1
Disseminated intravascular coagulation	1/126 (0.8%)	1	0/128 (0%)	0
Febrile neutropenia	11/126 (8.7%)	11	6/128 (4.7%)	6
Haemolysis	2/126 (1.6%)	2	0/128 (0%)	0
Haemolytic anaemia	1/126 (0.8%)	1	0/128 (0%)	0
Idiopathic thrombocytopenic purpura	1/126 (0.8%)	1	1/128 (0.8%)	1
Leukocytosis	1/126 (0.8%)	1	0/128 (0%)	0
Microangiopathic haemolytic anaemia	0/126 (0%)	0	1/128 (0.8%)	1
Neutropenia	0/126 (0%)	0	1/128 (0.8%)	1
Pancytopenia	6/126 (4.8%)	6	3/128 (2.3%)	4
Thrombocytopenia	4/126 (3.2%)	4	0/128 (0%)	0
Thrombotic microangiopathy	1/126 (0.8%)	1	0/128 (0%)	0
Cardiac disorders
Acute myocardial infarction	2/126 (1.6%)	2	0/128 (0%)	0
Angina pectoris	1/126 (0.8%)	1	0/128 (0%)	0
Atrial fibrillation	1/126 (0.8%)	1	0/128 (0%)	0
Cardiac arrest	0/126 (0%)	0	1/128 (0.8%)	1
Cardio-respiratory arrest	0/126 (0%)	0	2/128 (1.6%)	2
Cardiopulmonary failure	0/126 (0%)	0	1/128 (0.8%)	1
Myocardial infarction	0/126 (0%)	0	1/128 (0.8%)	1
Myocardial ischaemia	1/126 (0.8%)	1	0/128 (0%)	0
Myopericarditis	0/126 (0%)	0	1/128 (0.8%)	1
Postural orthostatic tachycardia syndrome	0/126 (0%)	0	1/128 (0.8%)	1
Pulseless electrical activity	0/126 (0%)	0	1/128 (0.8%)	1
Tachycardia	1/126 (0.8%)	1	1/128 (0.8%)	1
Eye disorders
Pupils unequal	0/126 (0%)	0	1/128 (0.8%)	1
Gastrointestinal disorders
Abdominal discomfort	1/126 (0.8%)	1	0/128 (0%)	0
Abdominal pain	2/126 (1.6%)	3	2/128 (1.6%)	2
Constipation	1/126 (0.8%)	1	0/128 (0%)	0
Diarrhoea	7/126 (5.6%)	9	7/128 (5.5%)	8
Gastrointestinal haemorrhage	6/126 (4.8%)	6	0/128 (0%)	0
Gastrooesophageal reflux disease	1/126 (0.8%)	1	0/128 (0%)	0
Gastropleural fistula	0/126 (0%)	0	1/128 (0.8%)	1
Haematemesis	1/126 (0.8%)	1	0/128 (0%)	0
Impaired gastric emptying	1/126 (0.8%)	1	0/128 (0%)	0
Lower gastrointestinal haemorrhage	0/126 (0%)	0	1/128 (0.8%)	1
Nausea	8/126 (6.3%)	10	7/128 (5.5%)	7
Oral pain	1/126 (0.8%)	1	0/128 (0%)	0
Pancreatitis acute	0/126 (0%)	0	2/128 (1.6%)	2
Peritonitis	0/126 (0%)	0	1/128 (0.8%)	1
Retroperitoneal haematoma	0/126 (0%)	0	1/128 (0.8%)	1
Small intestinal haemorrhage	0/126 (0%)	0	1/128 (0.8%)	1
Stomatitis	2/126 (1.6%)	2	1/128 (0.8%)	1
Vomiting	8/126 (6.3%)	8	8/128 (6.3%)	8
General disorders
Asthenia	0/126 (0%)	0	1/128 (0.8%)	1
Chills	1/126 (0.8%)	1	0/128 (0%)	0
Fatigue	2/126 (1.6%)	4	1/128 (0.8%)	1
Mucosal haemorrhage	1/126 (0.8%)	1	0/128 (0%)	0
Mucosal inflammation	4/126 (3.2%)	4	5/128 (3.9%)	5
Multi-organ failure	5/126 (4%)	5	1/128 (0.8%)	1
Oedema	0/126 (0%)	0	1/128 (0.8%)	1
Pain	1/126 (0.8%)	1	1/128 (0.8%)	1
Pyrexia	13/126 (10.3%)	14	15/128 (11.7%)	20
Hepatobiliary disorders
Cholecystitis	0/126 (0%)	0	1/128 (0.8%)	1
Cholecystitis acute	1/126 (0.8%)	1	0/128 (0%)	0
Cholecystitis chronic	1/126 (0.8%)	1	0/128 (0%)	0
Cholelithiasis	1/126 (0.8%)	1	0/128 (0%)	0
Cholestasis	2/126 (1.6%)	2	0/128 (0%)	0
Hepatic failure	0/126 (0%)	0	1/128 (0.8%)	1
Hyperbilirubinaemia	1/126 (0.8%)	1	0/128 (0%)	0
Portal hypertension	0/126 (0%)	0	1/128 (0.8%)	1
Venoocclusive liver disease	6/126 (4.8%)	6	1/128 (0.8%)	1
Immune system disorders
Acute graft versus host disease	1/126 (0.8%)	1	0/128 (0%)	0
Acute graft versus host disease in intestine	1/126 (0.8%)	2	3/128 (2.3%)	3
Chronic graft versus host disease	0/126 (0%)	0	3/128 (2.3%)	3
Cytokine release syndrome	2/126 (1.6%)	2	0/128 (0%)	0
Engraftment syndrome	0/126 (0%)	0	2/128 (1.6%)	2
Graft versus host disease	2/126 (1.6%)	2	5/128 (3.9%)	5
Graft versus host disease in lung	1/126 (0.8%)	1	0/128 (0%)	0
Serum sickness	1/126 (0.8%)	1	0/128 (0%)	0
Infections and infestations
Adenovirus infection	2/126 (1.6%)	2	0/128 (0%)	0
Appendicitis	2/126 (1.6%)	2	0/128 (0%)	0
Arthritis bacterial	1/126 (0.8%)	1	0/128 (0%)	0
Bacteraemia	3/126 (2.4%)	4	4/128 (3.1%)	4
Bacterial infection	1/126 (0.8%)	1	0/128 (0%)	0
Bacterial sepsis	1/126 (0.8%)	1	0/128 (0%)	0
Bronchitis	2/126 (1.6%)	3	0/128 (0%)	0
Candidiasis	1/126 (0.8%)	1	1/128 (0.8%)	1
Cellulitis	3/126 (2.4%)	4	4/128 (3.1%)	4
Clostridial infection	2/126 (1.6%)	2	5/128 (3.9%)	5
Clostridium difficile colitis	1/126 (0.8%)	1	2/128 (1.6%)	3
Corona virus infection	1/126 (0.8%)	1	0/128 (0%)	0
Cystitis viral	1/126 (0.8%)	1	1/128 (0.8%)	1
Cytomegalovirus chorioretinitis	2/126 (1.6%)	2	0/128 (0%)	0
Cytomegalovirus colitis	1/126 (0.8%)	1	1/128 (0.8%)	2
Cytomegalovirus infection	4/126 (3.2%)	4	0/128 (0%)	0
Cytomegalovirus viraemia	1/126 (0.8%)	1	4/128 (3.1%)	4
Encephalitis fungal	0/126 (0%)	0	1/128 (0.8%)	1
Encephalitis herpes	0/126 (0%)	0	1/128 (0.8%)	1
Enterobacter bacteraemia	2/126 (1.6%)	3	0/128 (0%)	0
Enterococcal bacteraemia	3/126 (2.4%)	3	1/128 (0.8%)	1
Enterococcal infection	1/126 (0.8%)	1	1/128 (0.8%)	1
Enterocolitis infectious	3/126 (2.4%)	4	1/128 (0.8%)	1
Epstein-Barr virus infection	2/126 (1.6%)	2	0/128 (0%)	0
Escherichia bacteraemia	1/126 (0.8%)	1	0/128 (0%)	0
Escherichia sepsis	1/126 (0.8%)	1	0/128 (0%)	0
Fungal abscess central nervous system	1/126 (0.8%)	1	0/128 (0%)	0
Fungal infection	1/126 (0.8%)	1	0/128 (0%)	0
Fusobacterium infection	1/126 (0.8%)	1	0/128 (0%)	0
Gastroenteritis	2/126 (1.6%)	3	1/128 (0.8%)	1
H1N1 influenza	0/126 (0%)	0	2/128 (1.6%)	2
Herpes zoster	1/126 (0.8%)	1	0/128 (0%)	0
Infection	0/126 (0%)	0	1/128 (0.8%)	1
Influenza	0/126 (0%)	0	1/128 (0.8%)	1
Klebsiella infection	1/126 (0.8%)	1	0/128 (0%)	0
Lobar pneumonia	0/126 (0%)	0	1/128 (0.8%)	2
Lung infection	1/126 (0.8%)	1	3/128 (2.3%)	3
Lung infection pseudomonal	0/126 (0%)	0	1/128 (0.8%)	1
Oral herpes	1/126 (0.8%)	1	1/128 (0.8%)	1
Parainfluenzae virus infection	2/126 (1.6%)	2	0/128 (0%)	0
Pneumocystis jiroveci pneumonia	0/126 (0%)	0	1/128 (0.8%)	1
Pneumonia	8/126 (6.3%)	9	14/128 (10.9%)	22
Pneumonia bacterial	1/126 (0.8%)	1	0/128 (0%)	0
Pneumonia cytomegaloviral	1/126 (0.8%)	1	1/128 (0.8%)	1
Pneumonia haemophilus	0/126 (0%)	0	1/128 (0.8%)	1
Pneumonia legionella	1/126 (0.8%)	1	0/128 (0%)	0
Pneumonia respiratory syncytial viral	2/126 (1.6%)	2	4/128 (3.1%)	4
Pneumonia staphylococcal	0/126 (0%)	0	1/128 (0.8%)	1
Pneumonia streptococcal	0/126 (0%)	0	1/128 (0.8%)	1
Pneumonia viral	0/126 (0%)	0	1/128 (0.8%)	1
Pseudomonal bacteraemia	0/126 (0%)	0	2/128 (1.6%)	2
Pyothorax	0/126 (0%)	0	1/128 (0.8%)	1
Respiratory syncytial virus infection	2/126 (1.6%)	2	1/128 (0.8%)	1
Rhinovirus infection	1/126 (0.8%)	1	1/128 (0.8%)	1
Sepsis	5/126 (4%)	6	13/128 (10.2%)	13
Septic shock	1/126 (0.8%)	1	4/128 (3.1%)	4
Sinusitis	1/126 (0.8%)	1	2/128 (1.6%)	2
Sinusitis bacterial	0/126 (0%)	0	1/128 (0.8%)	1
Skin infection	0/126 (0%)	0	2/128 (1.6%)	2
Staphylococcal bacteraemia	5/126 (4%)	5	0/128 (0%)	0
Staphylococcal infection	1/126 (0.8%)	1	0/128 (0%)	0
Staphylococcal sepsis	1/126 (0.8%)	1	0/128 (0%)	0
Streptococcal bacteraemia	1/126 (0.8%)	1	1/128 (0.8%)	1
Systemic candida	1/126 (0.8%)	1	0/128 (0%)	0
Systemic mycosis	1/126 (0.8%)	1	0/128 (0%)	0
Upper respiratory fungal infection	1/126 (0.8%)	1	0/128 (0%)	0
Urinary tract infection	1/126 (0.8%)	1	0/128 (0%)	0
Urinary tract infection bacterial	1/126 (0.8%)	1	0/128 (0%)	0
Urinary tract infection viral	1/126 (0.8%)	1	0/128 (0%)	0
Viraemia	0/126 (0%)	0	1/128 (0.8%)	1
Viral haemorrhagic cystitis	3/126 (2.4%)	4	0/128 (0%)	0
Zygomycosis	1/126 (0.8%)	1	0/128 (0%)	0
Injury, poisoning and procedural complications
Delayed engraftment	2/126 (1.6%)	2	0/128 (0%)	0
Femoral neck fracture	1/126 (0.8%)	1	0/128 (0%)	0
Foot fracture	0/126 (0%)	0	1/128 (0.8%)	1
Hepatic haematoma	1/126 (0.8%)	1	0/128 (0%)	0
Hip fracture	0/126 (0%)	0	1/128 (0.8%)	1
Infusion related reaction	6/126 (4.8%)	6	0/128 (0%)	0
Post procedural haemorrhage	1/126 (0.8%)	1	0/128 (0%)	0
Pubis fracture	0/126 (0%)	0	1/128 (0.8%)	1
Splenic rupture	1/126 (0.8%)	1	0/128 (0%)	0
Subdural haematoma	1/126 (0.8%)	1	0/128 (0%)	0
Transfusion related complication	1/126 (0.8%)	1	0/128 (0%)	0
Transplant failure	1/126 (0.8%)	1	0/128 (0%)	0
Investigations
Alanine aminotransferase increased	1/126 (0.8%)	1	0/128 (0%)	0
Aspartate aminotransferase increased	1/126 (0.8%)	1	0/128 (0%)	0
Blood bilirubin increased	1/126 (0.8%)	1	0/128 (0%)	0
Clostridium test positive	0/126 (0%)	0	3/128 (2.3%)	3
Hepatic enzyme abnormal	0/126 (0%)	0	1/128 (0.8%)	1
Hepatic enzyme increased	0/126 (0%)	0	1/128 (0.8%)	1
Human rhinovirus test positive	1/126 (0.8%)	1	0/128 (0%)	0
Legionella test positive	0/126 (0%)	0	1/128 (0.8%)	1
Liver function test abnormal	2/126 (1.6%)	2	0/128 (0%)	0
Polyomavirus test positive	1/126 (0.8%)	1	1/128 (0.8%)	1
Respiratory rate increased	1/126 (0.8%)	1	0/128 (0%)	0
Respiratory syncytial virus test positive	0/126 (0%)	0	1/128 (0.8%)	1
Weight decreased	2/126 (1.6%)	3	0/128 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/126 (0.8%)	1	0/128 (0%)	0
Dehydration	2/126 (1.6%)	2	2/128 (1.6%)	2
Diabetes mellitus	1/126 (0.8%)	1	1/128 (0.8%)	1
Failure to thrive	0/126 (0%)	0	1/128 (0.8%)	1
Fluid overload	1/126 (0.8%)	1	0/128 (0%)	0
Hyperglycaemia	1/126 (0.8%)	1	2/128 (1.6%)	2
Hyperkalaemia	1/126 (0.8%)	1	0/128 (0%)	0
Hyponatraemia	0/126 (0%)	0	1/128 (0.8%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/126 (0.8%)	1	0/128 (0%)	0
Back pain	2/126 (1.6%)	2	0/128 (0%)	0
Chondrocalcinosis pyrophosphate	0/126 (0%)	0	1/128 (0.8%)	1
Groin pain	1/126 (0.8%)	1	0/128 (0%)	0
Muscular weakness	3/126 (2.4%)	3	1/128 (0.8%)	1
Musculoskeletal chest pain	0/126 (0%)	0	1/128 (0.8%)	1
Myositis	0/126 (0%)	0	2/128 (1.6%)	2
Rhabdomyolysis	0/126 (0%)	0	1/128 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	4/126 (3.2%)	4	1/128 (0.8%)	1
Acute myeloid leukaemia	2/126 (1.6%)	2	1/128 (0.8%)	1
Acute myeloid leukemia, recurrent	14/126 (11.1%)	14	5/128 (3.9%)	5
Colon cancer metastatic	0/126 (0%)	0	1/128 (0.8%)	1
Endometrial cancer	0/126 (0%)	0	1/128 (0.8%)	1
Epstein-Barr virus associated lymphoproliferative disorder	4/126 (3.2%)	4	0/128 (0%)	0
Leukaemia	1/126 (0.8%)	1	0/128 (0%)	0
Leukaemia recurrent	2/126 (1.6%)	2	2/128 (1.6%)	2
Squamous cell carcinoma	1/126 (0.8%)	1	1/128 (0.8%)	1
Nervous system disorders
Somnolence	1/126 (0.8%)	1	0/128 (0%)	0
Acute disseminated encephalomyelitis	0/126 (0%)	0	1/128 (0.8%)	1
Aphasia	1/126 (0.8%)	1	0/128 (0%)	0
Cerebral haemorrhage	1/126 (0.8%)	1	0/128 (0%)	0
Cerebral infarction	0/126 (0%)	0	1/128 (0.8%)	1
Cerebrovascular accident	1/126 (0.8%)	1	0/128 (0%)	0
Coma	0/126 (0%)	0	1/128 (0.8%)	1
Convulsion	0/126 (0%)	0	1/128 (0.8%)	1
Dizziness	1/126 (0.8%)	1	1/128 (0.8%)	1
Encephalitis	1/126 (0.8%)	1	0/128 (0%)	0
Headache	2/126 (1.6%)	3	1/128 (0.8%)	1
Myelitis transverse	1/126 (0.8%)	1	0/128 (0%)	0
Optic neuritis	0/126 (0%)	0	1/128 (0.8%)	1
Syncope	1/126 (0.8%)	1	1/128 (0.8%)	1
Psychiatric disorders
Completed suicide	0/126 (0%)	0	1/128 (0.8%)	1
Confusional state	4/126 (3.2%)	4	1/128 (0.8%)	1
Delirium	0/126 (0%)	0	1/128 (0.8%)	1
Depression	0/126 (0%)	0	1/128 (0.8%)	1
Mental status changes	0/126 (0%)	0	5/128 (3.9%)	6
Psychotic disorder	0/126 (0%)	0	1/128 (0.8%)	1
Renal and urinary disorders
Cystitis haemorrhagic	1/126 (0.8%)	1	0/128 (0%)	0
Haematuria	1/126 (0.8%)	1	2/128 (1.6%)	2
Hydronephrosis	1/126 (0.8%)	1	0/128 (0%)	0
Renal failure	1/126 (0.8%)	1	2/128 (1.6%)	2
Renal failure acute	6/126 (4.8%)	6	4/128 (3.1%)	4
Renal tubular necrosis	0/126 (0%)	0	1/128 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/126 (0%)	0	3/128 (2.3%)	3
Chronic respiratory failure	0/126 (0%)	0	1/128 (0.8%)	1
Dyspnoea	3/126 (2.4%)	3	5/128 (3.9%)	5
Hydropneumothorax	0/126 (0%)	0	1/128 (0.8%)	1
Hypoxia	1/126 (0.8%)	1	2/128 (1.6%)	3
Idiopathic pneumonia syndrome	1/126 (0.8%)	1	3/128 (2.3%)	3
Obliterative bronchiolitis	0/126 (0%)	0	1/128 (0.8%)	1
Organising pneumonia	1/126 (0.8%)	1	1/128 (0.8%)	1
Oropharyngeal pain	1/126 (0.8%)	1	1/128 (0.8%)	1
Pharyngeal haemorrhage	0/126 (0%)	0	1/128 (0.8%)	1
Pleural effusion	1/126 (0.8%)	1	2/128 (1.6%)	2
Pneumonitis	1/126 (0.8%)	1	1/128 (0.8%)	1
Pulmonary alveolar haemorrhage	1/126 (0.8%)	1	0/128 (0%)	0
Pulmonary embolism	2/126 (1.6%)	2	1/128 (0.8%)	1
Pulmonary haemorrhage	2/126 (1.6%)	2	0/128 (0%)	0
Pulmonary oedema	1/126 (0.8%)	1	0/128 (0%)	0
Respiratory arrest	0/126 (0%)	0	2/128 (1.6%)	2
Respiratory distress	0/126 (0%)	0	1/128 (0.8%)	1
Respiratory failure	5/126 (4%)	5	3/128 (2.3%)	3
Wheezing	1/126 (0.8%)	1	0/128 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	0/126 (0%)	0	1/128 (0.8%)	1
Dermatitis allergic	1/126 (0.8%)	1	0/128 (0%)	0
Rash	1/126 (0.8%)	1	0/128 (0%)	0
Vascular disorders
Deep vein thrombosis	0/126 (0%)	0	1/128 (0.8%)	1
Embolism	0/126 (0%)	0	1/128 (0.8%)	1
Hypotension	7/126 (5.6%)	7	2/128 (1.6%)	2
Jugular vein thrombosis	0/126 (0%)	0	1/128 (0.8%)	1
Orthostatic hypotension	0/126 (0%)	0	1/128 (0.8%)	1
Other (Not Including Serious) Adverse Events
	US-ATG-F		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	125/126 (99.2%)		126/128 (98.4%)
Blood and lymphatic system disorders
Febrile neutropenia	34/126 (27%)	44	47/128 (36.7%)	48
Thrombocytopenia	22/126 (17.5%)	42	12/128 (9.4%)	29
Anaemia	14/126 (11.1%)	27	11/128 (8.6%)	21
Neutropenia	12/126 (9.5%)	22	8/128 (6.3%)	10
Cardiac disorders
Tachycardia	23/126 (18.3%)	24	3/128 (2.3%)	3
Sinus tachycardia	19/126 (15.1%)	19	5/128 (3.9%)	8
Gastrointestinal disorders
Nausea	54/126 (42.9%)	63	47/128 (36.7%)	56
Vomiting	38/126 (30.2%)	43	24/128 (18.8%)	27
Diarrhoea	36/126 (28.6%)	45	22/128 (17.2%)	28
Stomatitis	25/126 (19.8%)	26	26/128 (20.3%)	26
Abdominal pain	11/126 (8.7%)	11	4/128 (3.1%)	4
Dyspepsia	3/126 (2.4%)	3	11/128 (8.6%)	11
Constipation	2/126 (1.6%)	2	8/128 (6.3%)	8
General disorders
Mucosal inflammation	41/126 (32.5%)	44	41/128 (32%)	47
Pyrexia	57/126 (45.2%)	71	1/128 (0.8%)	2
Fatigue	33/126 (26.2%)	36	34/128 (26.6%)	34
Chills	50/126 (39.7%)	54	7/128 (5.5%)	7
Oedema peripheral	11/126 (8.7%)	11	3/128 (2.3%)	3
Pain	10/126 (7.9%)	10	2/128 (1.6%)	6
Infections and infestations
Cytomegalovirus infection	12/126 (9.5%)	16	18/128 (14.1%)	20
Cytomegalovirus viraemia	13/126 (10.3%)	19	10/128 (7.8%)	12
Epstein-Barr virus infection	14/126 (11.1%)	16	6/128 (4.7%)	7
Clostridial infection	5/126 (4%)	7	7/128 (5.5%)	8
Clostridium difficile colitis	11/126 (8.7%)	13	2/128 (1.6%)	3
Staphylococcal bacteraemia	9/126 (7.1%)	13	1/128 (0.8%)	1
Urinary tract infection	9/126 (7.1%)	9	3/128 (2.3%)	3
Epstein-Barr viraemia	8/126 (6.3%)	8	1/128 (0.8%)	1
Injury, poisoning and procedural complications
Infusion related reaction	16/126 (12.7%)	30	4/128 (3.1%)	6
Investigations
White blood cell count decreased	9/126 (7.1%)	15	5/128 (3.9%)	9
Blood bilirubin increased	9/126 (7.1%)	14	2/128 (1.6%)	3
Epstein-Barr virus test positive	7/126 (5.6%)	7	1/128 (0.8%)	3
Metabolism and nutrition disorders
Hyperglycaemia	10/126 (7.9%)	10	7/128 (5.5%)	9
Decreased appetite	7/126 (5.6%)	7	6/128 (4.7%)	6
Hypomagnesaemia	8/126 (6.3%)	8	1/128 (0.8%)	1
Nervous system disorders
Headache	38/126 (30.2%)	44	19/128 (14.8%)	22
Dizziness	8/126 (6.3%)	10	2/128 (1.6%)	2
Psychiatric disorders
Anxiety	13/126 (10.3%)	13	6/128 (4.7%)	6
Respiratory, thoracic and mediastinal disorders
Dyspnoea	22/126 (17.5%)	22	5/128 (3.9%)	6
Epistaxis	11/126 (8.7%)	12	1/128 (0.8%)	2
Cough	7/126 (5.6%)	7	0/128 (0%)	0
Skin and subcutaneous tissue disorders
Rash	31/126 (24.6%)	35	7/128 (5.5%)	7
Rash maculo-papular	7/126 (5.6%)	7	1/128 (0.8%)	1
Vascular disorders
Hypotension	32/126 (25.4%)	36	6/128 (4.7%)	7
Hypertension	16/126 (12.7%)	17	6/128 (4.7%)	6
Flushing	9/126 (7.1%)	9	2/128 (1.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.