Adult Acute Lymphoid Leukemia, Adult Acute Myeloid Leukemia, GVHD, Myelodysplastic Syndrome
Conditions
Keywords
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)
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.
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.
Interventions
BIOLOGICALUS-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
BIOLOGICALPlacebo
250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation
Sponsors
Neovii Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Australia, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 126 |
| Placebo 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation | 128 |
| Total | 254 |
Baseline characteristics
| Characteristic | US-ATG-F | Total | Placebo |
|---|---|---|---|
| Age, Customized 18 years to ≤40 years | 42 Participants | 85 Participants | 43 Participants |
| Age, Customized >40 years to 65 years | 84 Participants | 169 Participants | 85 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: BU-CY ALC ≤ 0.1 x 10^9 lymphocytes/L | 6 Participants | 8 Participants | 2 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: BU-CY ALC > 0.1 x 10^9 lymphocytes/L | 39 Participants | 70 Participants | 31 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: BU-CY Not tested | 2 Participants | 6 Participants | 4 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: CY-TBI ALC ≤ 0.1 x 10^9 lymphocytes/L | 22 Participants | 46 Participants | 24 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: CY-TBI ALC > 0.1 x 10^9 lymphocytes/L | 7 Participants | 18 Participants | 11 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: CY-TBI Not tested | 2 Participants | 4 Participants | 2 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: FLU-BU ALC ≤ 0.1 x 10^9 lymphocytes/L | 23 Participants | 38 Participants | 15 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: FLU-BU ALC > 0.1 x 10^9 lymphocytes/L | 18 Participants | 50 Participants | 32 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimen: FLU-BU Not tested | 7 Participants | 14 Participants | 7 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimens: BU-CY + FLU-BU ALC ≤ 0.1 x 10^9 lymphocytes/L | 29 Participants | 46 Participants | 17 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimens: BU-CY + FLU-BU ALC > 0.1 x 10^9 lymphocytes/L | 57 Participants | 120 Participants | 63 Participants |
| ALC at Study Day -3 by Conditioning Regimen Regimens: BU-CY + FLU-BU Not tested | 9 Participants | 20 Participants | 11 Participants |
| ALC at Study Day -3 Overall Study ALC ≤ 0.1 x 10^9 lymphocytes/L | 51 Participants | 92 Participants | 41 Participants |
| ALC at Study Day -3 Overall Study ALC > 0.1 x 10^9 lymphocytes/L | 64 Participants | 138 Participants | 74 Participants |
| ALC at Study Day -3 Overall Study Not tested | 11 Participants | 24 Participants | 13 Participants |
| Conditioning regimen Busulfan & cyclophosphamide (BU-CY) | 47 Participants | 84 Participants | 37 Participants |
| Conditioning regimen Cyclophosphamide & total body irradiation (CY-TBI) | 31 Participants | 68 Participants | 37 Participants |
| Conditioning regimen Fludarabine & busulfan (FLU-BU) | 48 Participants | 102 Participants | 54 Participants |
| Disease Acute lymphoid leukemia (ALL) | 23 Participants | 57 Participants | 34 Participants |
| Disease Acute myeloid leukemia (AML) | 83 Participants | 163 Participants | 80 Participants |
| Disease Biphenotypic AML/ALL | 1 Participants | 1 Participants | 0 Participants |
| Disease Myelodysplastic syndrome (MDS) | 19 Participants | 33 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants | 236 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) White | 117 Participants | 234 Participants | 117 Participants |
| Region of Enrollment Australia | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 124 Participants | 249 Participants | 125 Participants |
| Sex: Female, Male Female | 66 Participants | 115 Participants | 49 Participants |
| Sex: Female, Male Male | 60 Participants | 139 Participants | 79 Participants |
| Source of stem cells Bone marrow | 22 Participants | 49 Participants | 27 Participants |
| Source of stem cells No stem cell transplantation | 9 Participants | 9 Participants | 0 Participants |
| Source of stem cells Peripheral blood | 95 Participants | 196 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 125 / 126 | 126 / 128 |
| serious Total, serious adverse events | 98 / 126 | 90 / 128 |
Outcome results
Primary
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
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | 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 | 60 Participants |
| Placebo | 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 | 72 Participants |
Secondary
Disease-free Survival
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Disease-free Survival | 61 Participants |
| Placebo | Disease-free Survival | 49 Participants |
Secondary
Number of Participants With Acute GVHD Grade III-IV
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Acute GVHD Grade III-IV | 8 Participants |
| Placebo | Number of Participants With Acute GVHD Grade III-IV | 17 Participants |
Secondary
Number of Participants With Acute GVHD Grade II-IV
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Acute GVHD Grade II-IV | 28 Participants |
| Placebo | Number of Participants With Acute GVHD Grade II-IV | 53 Participants |
Secondary
Number of Participants With Acute GVHD Grade I-IV
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Acute GVHD Grade I-IV | 48 Participants |
| Placebo | Number of Participants With Acute GVHD Grade I-IV | 71 Participants |
Secondary
Number of Participants With Chronic GVHD Mild to Severe
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Chronic GVHD Mild to Severe | 18 Participants |
| Placebo | Number of Participants With Chronic GVHD Mild to Severe | 50 Participants |
Secondary
Number of Participants With Chronic GVHD Moderate to Severe
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Chronic GVHD Moderate to Severe | 13 Participants |
| Placebo | Number of Participants With Chronic GVHD Moderate to Severe | 45 Participants |
Secondary
Number of Participants With Chronic GVHD Severe
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Chronic GVHD Severe | 3 Participants |
| Placebo | Number of Participants With Chronic GVHD Severe | 16 Participants |
Secondary
Number of Participants With Relapse
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Relapse | 37 Participants |
| Placebo | Number of Participants With Relapse | 26 Participants |
Secondary
Number of Participants With Transplant Related Mortality
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Number of Participants With Transplant Related Mortality | 24 Participants |
| Placebo | Number of Participants With Transplant Related Mortality | 23 Participants |
Secondary
Overall Survival
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Overall Survival | 49 Participants |
| Placebo | Overall Survival | 36 Participants |
Secondary
Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD | 8 Participants |
| Placebo | Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD | 33 Participants |
Post Hoc
Acute GVHD Grade III-IV by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: CY-TBI | 3 Participants |
| US-ATG-F | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: BU-CY | 4 Participants |
| US-ATG-F | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: FLU-BU | 1 Participants |
| US-ATG-F | Acute GVHD Grade III-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 5 Participants |
| Placebo | Acute GVHD Grade III-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 15 Participants |
| Placebo | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: CY-TBI | 2 Participants |
| Placebo | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: FLU-BU | 10 Participants |
| Placebo | Acute GVHD Grade III-IV by Conditioning Regimen | Regimen: BU-CY | 5 Participants |
Post Hoc
Acute GVHD Grade II-IV by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: CY-TBI | 8 Participants |
| US-ATG-F | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: BU-CY | 12 Participants |
| US-ATG-F | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: FLU-BU | 8 Participants |
| US-ATG-F | Acute GVHD Grade II-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 20 Participants |
| Placebo | Acute GVHD Grade II-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 39 Participants |
| Placebo | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: CY-TBI | 14 Participants |
| Placebo | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: FLU-BU | 22 Participants |
| Placebo | Acute GVHD Grade II-IV by Conditioning Regimen | Regimen: BU-CY | 17 Participants |
Post Hoc
Acute GVHD Grade I-IV by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Acute GVHD Grade I-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 35 Participants |
| US-ATG-F | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: BU-CY | 19 Participants |
| US-ATG-F | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: CY-TBI | 13 Participants |
| US-ATG-F | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: FLU-BU | 16 Participants |
| Placebo | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: CY-TBI | 18 Participants |
| Placebo | Acute GVHD Grade I-IV by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 53 Participants |
| Placebo | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: FLU-BU | 30 Participants |
| Placebo | Acute GVHD Grade I-IV by Conditioning Regimen | Regimen: BU-CY | 23 Participants |
Post Hoc
Chronic GVHD Mild to Severe by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 11 Participants |
| US-ATG-F | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: BU-CY | 6 Participants |
| US-ATG-F | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: CY-TBI | 7 Participants |
| US-ATG-F | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: FLU-BU | 5 Participants |
| Placebo | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: CY-TBI | 16 Participants |
| Placebo | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 34 Participants |
| Placebo | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: FLU-BU | 20 Participants |
| Placebo | Chronic GVHD Mild to Severe by Conditioning Regimen | Regimen: BU-CY | 14 Participants |
Post Hoc
Chronic GVHD Moderate to Severe by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: CY-TBI | 5 Participants |
| US-ATG-F | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: BU-CY | 6 Participants |
| US-ATG-F | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: FLU-BU | 2 Participants |
| US-ATG-F | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 8 Participants |
| Placebo | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 32 Participants |
| Placebo | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: CY-TBI | 13 Participants |
| Placebo | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: FLU-BU | 19 Participants |
| Placebo | Chronic GVHD Moderate to Severe by Conditioning Regimen | Regimen: BU-CY | 13 Participants |
Post Hoc
Chronic GVHD Severe by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Chronic GVHD Severe by Conditioning Regimen | Regimen: FLU-BU | 1 Participants |
| US-ATG-F | Chronic GVHD Severe by Conditioning Regimen | Regimen: CY-TBI | 1 Participants |
| US-ATG-F | Chronic GVHD Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 2 Participants |
| US-ATG-F | Chronic GVHD Severe by Conditioning Regimen | Regimen: BU-CY | 1 Participants |
| Placebo | Chronic GVHD Severe by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 11 Participants |
| Placebo | Chronic GVHD Severe by Conditioning Regimen | Regimen: BU-CY | 4 Participants |
| Placebo | Chronic GVHD Severe by Conditioning Regimen | Regimen: CY-TBI | 5 Participants |
| Placebo | Chronic GVHD Severe by Conditioning Regimen | Regimen: FLU-BU | 7 Participants |
Post Hoc
Disease-free Survival by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Disease-free Survival by Conditioning Regimen | Regimen: CY-TBI | 21 Participants |
| US-ATG-F | Disease-free Survival by Conditioning Regimen | Regimen: BU-CY | 15 Participants |
| US-ATG-F | Disease-free Survival by Conditioning Regimen | Regimen: FLU-BU | 25 Participants |
| US-ATG-F | Disease-free Survival by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 40 Participants |
| Placebo | Disease-free Survival by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 36 Participants |
| Placebo | Disease-free Survival by Conditioning Regimen | Regimen: CY-TBI | 13 Participants |
| Placebo | Disease-free Survival by Conditioning Regimen | Regimen: FLU-BU | 25 Participants |
| Placebo | Disease-free Survival by Conditioning Regimen | Regimen: BU-CY | 11 Participants |
Post Hoc
Grade III-IV Acute GVHD-free, GRFS
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Grade III-IV Acute GVHD-free, GRFS | 72 Participants |
| Placebo | Grade III-IV Acute GVHD-free, GRFS | 85 Participants |
Post Hoc
Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: CY-TBI | 23 Participants |
| US-ATG-F | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: BU-CY | 23 Participants |
| US-ATG-F | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: FLU-BU | 26 Participants |
| US-ATG-F | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 49 Participants |
| Placebo | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 64 Participants |
| Placebo | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: CY-TBI | 21 Participants |
| Placebo | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: FLU-BU | 42 Participants |
| Placebo | Grade III-IV Acute GVHD-free GRFS by Conditioning Regimen | Regimen: BU-CY | 22 Participants |
Post Hoc
Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS)
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) | 70 Participants |
| Placebo | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) | 81 Participants |
Post Hoc
Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: CY-TBI | 23 Participants |
| US-ATG-F | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 47 Participants |
| US-ATG-F | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: BU-CY | 21 Participants |
| US-ATG-F | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: FLU-BU | 26 Participants |
| Placebo | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: FLU-BU | 39 Participants |
| Placebo | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: BU-CY | 22 Participants |
| Placebo | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 61 Participants |
| Placebo | Moderate to Severe Chronic GVHD-free, Relapse-free Survival (GRFS) by Conditioning Regimen | Regimen: CY-TBI | 20 Participants |
Post Hoc
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
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| US-ATG-F | 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 | 63 Participants |
| Placebo | 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 | 86 Participants |
Post Hoc
Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: CY-TBI | 20 Participants |
| US-ATG-F | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: BU-CY | 18 Participants |
| US-ATG-F | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: FLU-BU | 22 Participants |
| US-ATG-F | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 40 Participants |
| Placebo | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: BU-CY | 21 Participants |
| Placebo | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 56 Participants |
| Placebo | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: CY-TBI | 16 Participants |
| Placebo | Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD or Death From Any Cause by Conditioning Regimen | Regimen: FLU-BU | 35 Participants |
Post Hoc
Overall Survival by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Overall Survival by Conditioning Regimen | Regimen: CY-TBI | 17 Participants |
| US-ATG-F | Overall Survival by Conditioning Regimen | Regimen: BU-CY | 12 Participants |
| US-ATG-F | Overall Survival by Conditioning Regimen | Regimen: FLU-BU | 20 Participants |
| US-ATG-F | Overall Survival by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 32 Participants |
| Placebo | Overall Survival by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 28 Participants |
| Placebo | Overall Survival by Conditioning Regimen | Regimen: CY-TBI | 8 Participants |
| Placebo | Overall Survival by Conditioning Regimen | Regimen: FLU-BU | 20 Participants |
| Placebo | Overall Survival by Conditioning Regimen | Regimen: BU-CY | 8 Participants |
Post Hoc
Relapse by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Relapse by Conditioning Regimen | Regimen: FLU-BU | 18 Participants |
| US-ATG-F | Relapse by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 26 Participants |
| US-ATG-F | Relapse by Conditioning Regimen | Regimen: CY-TBI | 11 Participants |
| US-ATG-F | Relapse by Conditioning Regimen | Regimen: BU-CY | 8 Participants |
| Placebo | Relapse by Conditioning Regimen | Regimen: BU-CY | 7 Participants |
| Placebo | Relapse by Conditioning Regimen | Regimen: FLU-BU | 13 Participants |
| Placebo | Relapse by Conditioning Regimen | Regimen: CY-TBI | 6 Participants |
| Placebo | Relapse by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 20 Participants |
Post Hoc
Transplant-related Mortality by Conditioning Regimen
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
Population: Analysis of patients who received a specific conditioning regimen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| US-ATG-F | Transplant-related Mortality by Conditioning Regimen | Regimen: CY-TBI | 10 Participants |
| US-ATG-F | Transplant-related Mortality by Conditioning Regimen | Regimen: BU-CY | 7 Participants |
| US-ATG-F | Transplant-related Mortality by Conditioning Regimen | Regimen: FLU-BU | 7 Participants |
| US-ATG-F | Transplant-related Mortality by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 14 Participants |
| Placebo | Transplant-related Mortality by Conditioning Regimen | Regimens: BU-CY + FLU-BU | 16 Participants |
| Placebo | Transplant-related Mortality by Conditioning Regimen | Regimen: CY-TBI | 7 Participants |
| Placebo | Transplant-related Mortality by Conditioning Regimen | Regimen: FLU-BU | 12 Participants |
| Placebo | Transplant-related Mortality by Conditioning Regimen | Regimen: BU-CY | 4 Participants |