Abatacept as GVHD Prophylaxis Phase 2

• Sponsor: Boston Children's Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01743131
• Collaborator: FDA Office of Orphan Products Development (U.S. Fed)
• Enrollment: 186
• Locations: 14
• Arms: 2
• Duration (Months): 120
• Patients Per Site: 13.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase II multi-center, randomized, double blind, placebo-controlled trial.

The investigators are doing this study to see if a new drug, abatacept, can be used together with a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate to provide better protection against Acute Graft versus Host Disease (aGvHD) without causing more infections.

Condition or Disease	Intervention/Treatment	Phase
Graft vs Host Disease; Malignancy	Drug: Abatacept; Drug: placebo	Phase 2

Detailed Description

Acute Graft versus Host Disease (aGvHD) is the most deadly complication facing children who have allogeneic hematopoietic stem cell transplant (HSCT). aGvHD occurs, in large part, because the T cells in the bone marrow graft do not "accept" the presence of the transplant recipient's cells. They mount a severe, debilitating, and often deadly attack against the recipient, striking the skin, the liver, and the gastrointestinal track, most prominently. For patients receiving bone marrow from an unrelated donor, the rate of aGvHD can reach as high as 80%, with up to half of patients dying from this complication. Given the lack of success in preventing aGvHD with current therapies, novel therapies to prevent this disease are desperately needed.

Hypothesis and Aims: This trial is being conducted as a step toward testing the long-term hypothesis that the costimulation blockade agent abatacept can be added to a standard acute graft-versus-host disease (aGvHD) prophylaxis regimen (which includes a calcineurin inhibitor (CNI) and methotrexate), to improve disease-free survival after unrelated hematopoietic stem cell transplantation (HSCT) for patients with hematologic malignancies. As a phase II study, the overall aim of this trial is to make a preliminary assessment of abatacept's clinical safety and efficacy using short-term outcomes. Thus, this trial is designed to test two hypotheses:

1. A primary hypothesis that the addition of abatacept to calcineurin inhibition + methotrexate can decrease the incidence of early-onset (before day 100 post-transplant) severe (grades 3-4) aGvHD.

2. A secondary hypothesis that its addition will not hinder post-transplant reconstitution of protective immunity against latent viruses.

To test these two hypotheses, this study will have the following Specific Aims.

Specific Aim #1: To conduct a multicenter Phase II, randomized, double-blind, placebo controlled trial to assess the impact of abatacept on the incidence of aGVHD and its biology. To make this assessment patients will be randomized either to standard aGVHD prophylaxis with a CNI, methotrexate and placebo or to investigational prophylaxis with a CNI, methotrexate and abatacept. Correlative immunology studies will be performed to elucidate abatacept's effects on the graft-versus-host response.

Specific Aim #2: To assess the impact of abatacept on post-transplant reconstitution of protective immunity against viruses. This will involve monitoring the longitudinal recovery of lymphocyte subsets and virus-specific immunity, using tetramer analysis and viral stimulation assays. It will also involve monitoring viral infection and disease.

Background and Rationale:

The Unmet Need: Allogeneic HSCT is an effective treatment for aggressive leukemias and other hematological malignancies, often representing the only option for cure. However, some of its benefit, especially in the case of unrelated donor transplantation, is off-set by a high rate of transplant-related mortality (approximately 30% of recipients of unrelated donor transplantation will die of transplant-related complications) stemming largely from severe aGVHD and infection. 1-7 aGvHD occurs when reconstituting donor T cells8 become activated against recipient tissues.9 This activation can result in severe immune-mediated tissue damage to the host, with the skin, liver and GI tract being the most common targets. aGvHD-mediated damage to these vital organs can result in significant morbidity, and in death. While whole-scale T cell depletion of the allograft can successfully reduce rates of aGvHD, patients receiving T cell-depleted grafts exhibit profound defects in protective immunity, and often die of infection or relapse of their primary disease.10-12 This has created an unmet clinical need for a strategy that more effectively prevents severe aGvHD while preserving the transplant recipient's protective immune response.

Targeting T cell costimulation to prevent aGvHD: The immune activation observed in aGvHD bears close resemblance to the immune activation that occurs during both organ rejection and autoimmunity. Studies in these diseases have led to the development of a new class of agents, called 'costimulation blockade' reagents, which specifically target activated T cells and block their ability to become fully activated effector cells. 13 One of the most studied of the costimulatory pathways is the CD28:CD80/86 receptor:coreceptor interaction.14 Considerable work on this pathway has been accomplished, and has demonstrated the efficacy of inhibition of CD28:CD80/86 signaling in inhibiting T cell-mediated immune activation. The first CD80/86-directed costimulation blockade agent, CTLA4Ig, or 'abatacept,' is approved for use in rheumatoid arthritis, both in adults and in children older than 6 years.15-18 The experience with abatacept from 3 large randomized, placebo-controlled clinical trials, two in adults with rheumatoid arthritis and one in children with juvenile idiopathic arthritis (ages 6 and older) indicates that it is a safe agent.19-21 In these three trials, abatacept was dosed at 10 mg/kg and was administered IV on day 1, 15, 29 (one trial used day 30) and then every 28 days for a total of 6 to 10 months of total treatment. Collectively, most patients also received weekly, oral, low-dose methotrexate and low dose prednisone concurrently. In these trials, abatacept was well tolerated. Acutely, infusional reactions were rare and mild and occurred at rates that did not differ significantly from those with placebo. Abatacept was not associated with any hematologic, renal, cardiac, pulmonary, hepatic or neurologic abnormalities. Similarly, the rates of both total and serious adverse events were low, and did not differ from those with placebo. Abatacept has been shown to be safe, even in extended open label trials,22,23 not associated with excessive PTLD or other malignancies. 22-25 However, chronically-treated patients did experience a slightly higher risk of infections. 22,24,25 Phase III studies of a second-generation, higher avidity abatacept analog, belatacept (which is identical to abatacept except for two amino acid substitutions) have demonstrated efficacy in preventing renal transplant rejection. 26,27 Patients who received 10mg/kg of belatacept on days 1, 5, 14, 28, and every 28 days thereafter demonstrated improved renal function compared to those receiving cyclosporine, and similar graft survival.26,27 These results have led to the FDA approval of belatacept for a renal transplant indication. While overall rates of patient death, infection and serious infection in patients receiving belatacept were not different than in those receiving traditional immunosuppression,26,28 belatacept was associated with a statistically-significant increased rate of EBV-associated PTLD compared to cyclosporine-based immunosuppression (especially in patients that were EBV sero-negative prior to transplant).26,28 This observation raises an important question about the negative impact that belatacept and related compounds may have on protective immune responses to latent viruses. Rates of PTLD were much lower in EBV sero-positive patients,26,28 suggesting that any defect in protective immunity induced by belatacept may be more significant in the setting of primary EBV infection than during EBV reactivation. These observations underscore the critical importance of evaluating novel immunosuppressive strategies for their impact both on alloreactivity and on the post-transplant protective immune response.

Prior to our work, abatacept had not been tested for its ability to prevent GvHD in BMT patients. However, there was considerable evidence from murine models to suggest that it might be an active compound against the immune activation that occurs during GvHD.29-33 In addition, our research group developed a non-human primate model of GvHD 34 and used this model to demonstrate that an abatacept-containing immunosuppressive regimen could significantly protect against the development of primate GvHD. 34 These results, along with the clinical evidence for efficacy of abatacept and belatacept in both autoimmunity and solid organ transplantation provided the rationale for the development of a first-in-disease feasibility trial of abatacept for GvHD prevention (Clinical Trials.org #NCT01012492). This trial, which has now completed enrollment, has documented encouraging early results with respect to both the safety and efficacy of abatacept for GvHD prevention (Kean et al., ASH 2011). These results have led to the creation of the current Phase II clinical trial of abatacept for prevention of severe aGvHD.

Research Design and Methods Study Design: This will be a phase II, multi-center, randomized, double-blind, placebo-controlled trial.

Study Population, Subject Recruitment and Selection: Patients will be recruited from the Children's Healthcare of Atlanta Pediatric Blood and Marrow Transplant Program, the Emory University Adult Blood and Marrow Transplant Program, the University of Florida Adult Blood and Marrow Transplant Program, the Seattle Cancer Consortium including University of Washington, Seattle Children's Hospital, Seattle Cancer Care Alliance and from participating centers in the Pediatric Blood and Marrow Transplant Consortium (PBMTC). A total of 40 randomized 7/8 HLA matched patients and 140 8/8 HLA matched patients will be enrolled on this study. Patients who are enrolled, but determined to be Assignment Failures before receiving study drug/placebo will be replaced. 7/8 HLA matched patients enrolled prior to Protocol Amendment 4 and who were randomized to the study drug/placebo arm are not counted in either group of 40 or 140.

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Abatacept Combined With a Calcineurin Inhibitor and Methotrexate for Graft Versus Host Disease Prophylaxis: A Randomized Controlled Trial
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Jun 1, 2018
• Anticipated Study Completion Date: Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Standard GVHD Prophylxis + Placebo Standard GVHD prophylaxis and placebo. Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Drug: placebo
Experimental: Standard GVHD Prophylxis + Abatacept Standard GVHD prophylaxis and abatacept (investigational product). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Drug: Abatacept; Arm B-investigational prophylaxis with abatacept, a calcineurin inhibitor and methotrexate; Other Names: Orencia

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Cumulative Incidence of Severe aGVHD at Day +100 Post-transplant [First 100 days after transplant]

   The primary analysis will consist of estimating the cumulative incidence of severe aGVHD at day +100 post-transplant in the standard and investigational study arms. All registered patients will be considered for this analysis. The primary null hypothesis of the study is that there will be no difference in severe aGVHD between the investigational and standard GVHD prophylaxis arms. The primary outcome will be assessed in a final analysis to be performed after the last enrolled patient has been followed for 100 days post-transplant. The cumulative incidence and confidence interval will be calculated. The cumulative incidence will be compared between treatment arms using logistic regression models. Relapse will be considered a competing risk for aGVHD to negate the effect of measures, such as withdrawal of immune suppression and donor-lymphocyte infusion, often used in response to relapse.

Secondary Outcome Measures

1. A Cumulative Incidence of Serious Infection, Engraftment, Relapse, and Overall Survival Will be Computed. [5 years post transplant]

   A cumulative incidence of infection, serious infection, CMV viremia, CMV invasive disease, EBV viremia, PTLD, BK viremia and disease, adenovirus viremia and disease, engraftment of: neutrophils, platelets, lymphocyte count, total T cell counts, CD4+ T cell counts, and CD8+ T cell counts, secondary graft failure, graft rejection, all grades of early and late aGvHD, overlap syndrome, chronic GvHD, RRT, TRM, DFS, immunosuppression-free survival, immunosuppressive-free/relapse-free survival, relapse, and OS.

2. Percentage of Participants With Severe (Grade III-IV) aGVHD Free Survival (GFS) up to Day +180 [First 180 days after transplant]

   To compare severe (Grade III-IV) aGVHD free survival (GFS) up to Day 180 post-transplantation between the abatacelpt + standard GVHD prophylaxis and standard GVHD prophylaxis regimen. The aGVHD events in this definition of GFS are the adjudicated grade (III-IV) aGVHD events. (This is a pre-determined endpoint for the 8/8 cohort and a retrospective endpoint for the 7/8 cohort).

3. Rate of Severe (Grade III-IV) aGVHD (Based on Adjudicated aGVHD Events) up to Day +180 [First 180 days after transplant]

   To compare the cumulative incidence of severe (grade III-IV) aGVHD (based on adjudicated aGVHD events) up to Day 180 post-transplant between the abatacept + standard GVHD prophylaxis and standard GVHD prophylaxis regimen. (This is a pre-determined endpoint for the 8/8 cohort and a retrospective endpoint for the 7/8 cohort).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must be at least 6 years old and weigh 20 kg.

2. Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. The use of mismatched donors in which disparity is only in the host versus graft direction (because of recipient homozygosity) is discouraged because of the potentially heightened risk for graft rejection. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.

3. All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

4. Must have a high risk hematologic malignancy as defined below:

5. Acute myeloid leukemia (AML).

6. Myelodysplastic syndrome

(i) Adult patients (≥21 years) must meet criteria for intermediate, high or very high-risk disease based on the World Health Organization classification based prognostic scoring system.

Intermediate risk (2 points), high risk (3-4 points), very high risk (4-5 points)

• RA = refractory anemia, RARS = refractory anemia with ringed sideroblasts, RCMD = refractory cytopenia with multilineage dysplasia, RCMD-RS = refractory cytopenia with multilineage dysplasia and ringed sideroblasts, RAEB-1 = refractory anemia with excess of blasts-1 (5-9% blasts), RAEB-2 = refractory anemia with excess of blasts-2 (10-19% blasts).

• *Karyotype: Good = normal, -Y, del(5q), del(20q), Poor = complex (≥ 3 abnormalities), chromosome 7 anomalies, Intermediate = other abnormalities.

• *RBC transfusion requirement = having ≥ 1 RBC transfusion every 8 weeks over a 4-month period.

(ii) Pediatric patients with MDS, regardless of subtype, will be eligible.

(c) Acute lymphoblastic leukemia (ALL). (i) Given the poor prognosis of adults (≥21 years) with ALL, adults in 1st or greater complete remission will be eligible.. CR is defined as an M1 marrow (<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions (ii) Given the generally good prognosis of children (<21 years) with ALL, they will have to meet one of the criteria listed below. Additionally, children who are enrolled on a COG ALL trial for newly diagnosed or relapsed disease will have to meet the criteria for BMT outlined in that trial. CR is defined as an M1 marrow (<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions.

1. In 1st complete remission with a very high risk for relapse.

2. Haplodiploidy (<44 chromosomes)

3. 1% residual marrow blasts by flow cytometry at the end of induction.

4. 0.01% residual marrow blasts by flow cytometry at the end of consolidation.

5. Early T-Cell Precursor (ETP) phenotype

6. In 2nd complete remission with B-lineage disease after a marrow relapse occurring less than 36 months from diagnosis.

7. In 2nd complete remission with T-lineage disease or Ph+ disease after a marrow relapse occurring at any time.

8. In a 2nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than 18 months from diagnosis.

9. In 3rd or greater complete remission after a marrow or extramedullary relapse

(d) Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission (CR) or partial remission (PR). Cr will be defined as an M1 marrow (<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. CR without platelet recovery (CRp) will be considered complete remissions.) PR will be defined as an M2 marrow (5-19% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L.).

(e) Chronic myelogenous leukemia (CML). (i) Chronic phase with resistance to tyrosine kinase inhibitors. (ii) accelerated phase (development of cytogenetic abnormality in addition to t(9:22), blood blast percentage ≥10, blood basophil percentage ≥20, platelet count <100,000 X 109/L) (iii) blast crisis. (iv) 2nd or greater chronic phase.

(f) Acute Lymphoblastic Lymphoma in 2nd or greater complete remission. Complete remission includes confirmed complete response (CR) defined as the disappearance of all evidence of disease from all sites for at least 4 weeks. Bone marrow and CSF must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Imaging should include PET scanning. CR will also include unconfirmed complete responses defined as a residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by > 75% in sum of the products of the greatest perpendicular diameters (SPD), or any residual lesions in organs that have decreased by > 75%, with a negative PET scan, negative bone marrow and CSF.

(g) Peripheral T cell lymphoma (PTCL).

(h) Chronic lymphocytic leukemia (CLL) (i) Newly diagnosed disease with 17p- (ii) Disease beyond first CR that has been treated with a fludarabine containing regimen.

(i) Chronic myelomonocytic leukemia.

(j) Atypical (BCR-ABL negative) chronic myelogenous leukemia

(k) Hodgkin lymphoma that has recurred or progressed after an autologous BMT. Disease must be chemosensitive; salvage chemotherapy must produce at least a partial response.

(l) Non-Hodgkin lymphomas that has recurred or progressed after an autologous BMT.

Exclusion Criteria:

1. Prior allogeneic HSCT.

2. The patient is enrolled on a COG trial that uses criteria for unrelated donor HSCT, which conflict with our eligibility criteria.

3. The patient is enrolled on a COG trial that utilizes unrelated donor HSCT and requires that patients be transplanted using an approach specified by the protocol that is in conflict with the approach specified in this protocol.

4. Availability of a willing and suitable HLA identical related donor.

5. Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.

6. HIV infection.

7. Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.

8. Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.

9. Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.

10. Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.

11. Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers will not be excluded.

12. Known inherited or constitutional predisposition to cancer including, but not limited to Li-Fraumeni syndrome, Down syndrome and BRCA1 and BRCA2 mutations.

13. Incompletely treated active tuberculosis Infection.

14. Pregnancy (positive serum b-HCG) or breastfeeding.

15. Estimated GFR of < 50 mL/min/1.73m2.

16. Cardiac ejection fraction < 50.

17. bilirubin > 2 × upper limit of normal or ALT > 4 × upper limit of normal or unresolved veno-occlusive disease.

18. Pulmonary disease with FVC, FEV1 or DLCO parameters <45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.

19. Karnofsky performance score or Lansky Play-Performance Scale score <80

20. Presence of antibodies to a mismatched donor HLA antigen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	University of Florida	Gainesville	Florida	United States	32610
6	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia	United States	30322
7	Emory University/Winship Cancer Center	Atlanta	Georgia	United States	30322
8	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
9	University of Michigan	Ann Arbor	Michigan	United States	48109
10	Washington University	Saint Louis	Missouri	United States	63141
11	Michael Grimley	Cincinnati	Ohio	United States	45229
12	University of Utah	Salt Lake City	Utah	United States	84113
13	Seattle Cancer Care Alliance	Seattle	Washington	United States	98101
14	Children's and Women's Health Center of BC	Vancouver	British Columbia	Canada	V6H 3V4

Sponsors and Collaborators

• Boston Children's Hospital
• FDA Office of Orphan Products Development

Investigators

• Principal Investigator: Leslie Kean, MD, PhD, Boston Children's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 30, 2019

More Information

Publications

None provided.

• Responsible Party: Leslie Kean, MD, PhD, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT01743131
• Other Study ID Numbers: IRB00058187; Abatacept Phase 2, Aba2; R01FD004099
• First Posted: Dec 6, 2012
• Last Update Posted: Aug 4, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Graft vs Host Disease; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	All 7/8 patients are compared to a historical control group (127 controls) from the Center for International Blood and Marrow Research (CIBMTR) registry. One 7/8 patient was randomized to receive placebo and was removed from data analysis. 186 patients were enrolled and 185 were included in analysis (313 - 127 -1 = 185).

Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept	Matched Unrelated Donor - Randomized to Placebo	Mismatched Unrelated Donor - Received Abatacept	Mismatched Unrelated Donor - Received Placebo	Mismatched Unrelated Donor - CIBMTR Control (No ATG)
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	CIBMTR Control cohort - Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.
Period Title: Overall Study
STARTED	73	69	43	1	127
Not Included in Analysis	0	0	0	1	0
COMPLETED	73	69	43	1	127
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept	Matched Unrelated Donor - Randomized to Placebo	Mismatched Unrelated Donor - Received Abatacept	Mismatched Unrelated Donor - CIBMTR Control (No ATG)	Total
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	CIBMTR Control cohort - Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Total of all reporting groups
Overall Participants	73	69	43	127	312
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	44.1	41	39.0	45	44.2
Age, Customized (number of patients) [Number]
Age > 21 year	57	52	25	88	222
Sex/Gender, Customized (number of patients) [Number]
Male/Male	30	24	16	36	106
Male/Female	14	17	11	15	57
Female/Male	11	13	9	24	57
Female/Female	18	15	7	17	57
unknown	0	0	0	35	35
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 5.5%	2 2.9%	7 16.3%	0 0%	13 4.2%
Not Hispanic or Latino	68 93.2%	66 95.7%	36 83.7%	0 0%	170 54.5%
Unknown or Not Reported	1 1.4%	1 1.4%	0 0%	127 100%	129 41.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.4%	0 0%	1 2.3%	0 0%	2 0.6%
Asian	4 5.5%	2 2.9%	2 4.7%	4 3.1%	12 3.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 4.1%	2 2.9%	7 16.3%	4 3.1%	16 5.1%
White	63 86.3%	60 87%	31 72.1%	105 82.7%	259 83%
More than one race	1 1.4%	2 2.9%	0 0%	0 0%	3 1%
Unknown or Not Reported	1 1.4%	3 4.3%	2 4.7%	14 11%	20 6.4%
Region of Enrollment (participants) [Number]
United States	73 100%	69 100%	43 100%	127 100%	312 100%
Disease (participants) [Number]
Acute Myeloid Leukemia	30 41.1%	22 31.9%	15 34.9%	54 42.5%	123 39.4%
Acute Lymphocytic Leukemia	24 32.9%	23 33.3%	9 20.9%	26 20.5%	82 26.3%
Myelodysplastic Syndrome	15 20.5%	12 17.4%	11 25.6%	42 33.1%	80 25.6%
Chronic Myeloid Leukemia	1 1.4%	5 7.2%	4 9.3%	4 3.1%	14 4.5%
Hodgkin Lymphoma	1 1.4%	1 1.4%	1 2.3%	1 0.8%	4 1.3%
Other	2 2.7%	6 8.7%	3 7%	0 0%	11 3.5%
Karnofsky/Lansky Performance Status (participants) [Number]
Number [participants]	52 71.2%	52 75.4%	32 74.4%	95 74.8%	231 74%
Conditioning Regimen (participants) [Number]
Busulfan/Cyclophosphamide	28 38.4%	21 30.4%	13 30.2%	28 22%	90 28.8%
TBI/Cyclophosphamide	20 27.4%	26 37.7%	11 25.6%	37 29.1%	94 30.1%
Fludarabine/Melphalan	18 24.7%	20 29%	11 25.6%	15 11.8%	64 20.5%
Busulfan/Fludarabine	7 9.6%	2 2.9%	8 18.6%	38 29.9%	55 17.6%
Other	0 0%	0 0%	0 0%	9 7.1%	9 2.9%
Graft Type (participants) [Number]
Peripheral Blood	40 54.8%	43 62.3%	22 51.2%	79 62.2%	184 59%
Bone Marrow	33 45.2%	26 37.7%	21 48.8%	48 37.8%	128 41%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Cumulative Incidence of Severe aGVHD at Day +100 Post-transplant
Description	The primary analysis will consist of estimating the cumulative incidence of severe aGVHD at day +100 post-transplant in the standard and investigational study arms. All registered patients will be considered for this analysis. The primary null hypothesis of the study is that there will be no difference in severe aGVHD between the investigational and standard GVHD prophylaxis arms. The primary outcome will be assessed in a final analysis to be performed after the last enrolled patient has been followed for 100 days post-transplant. The cumulative incidence and confidence interval will be calculated. The cumulative incidence will be compared between treatment arms using logistic regression models. Relapse will be considered a competing risk for aGVHD to negate the effect of measures, such as withdrawal of immune suppression and donor-lymphocyte infusion, often used in response to relapse.
Time Frame	First 100 days after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept	Matched Unrelated Donor - Randomized to Placebo	Mismatched Unrelated Donor - Received Abatacept	Mismatched Unrelated Donor - CIBMTR Control (No ATG)
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	CIBMTR Control cohort - Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.
Measure Participants	73	69	43	127
Number (95% Confidence Interval) [percentage of participants]	6.8 9.3%	14.8 21.4%	2.2 5.1%	30.2 23.8%

2. Secondary Outcome

Title	A Cumulative Incidence of Serious Infection, Engraftment, Relapse, and Overall Survival Will be Computed.
Description	A cumulative incidence of infection, serious infection, CMV viremia, CMV invasive disease, EBV viremia, PTLD, BK viremia and disease, adenovirus viremia and disease, engraftment of: neutrophils, platelets, lymphocyte count, total T cell counts, CD4+ T cell counts, and CD8+ T cell counts, secondary graft failure, graft rejection, all grades of early and late aGvHD, overlap syndrome, chronic GvHD, RRT, TRM, DFS, immunosuppression-free survival, immunosuppressive-free/relapse-free survival, relapse, and OS.
Time Frame	5 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percentage of Participants With Severe (Grade III-IV) aGVHD Free Survival (GFS) up to Day +180
Description	To compare severe (Grade III-IV) aGVHD free survival (GFS) up to Day 180 post-transplantation between the abatacelpt + standard GVHD prophylaxis and standard GVHD prophylaxis regimen. The aGVHD events in this definition of GFS are the adjudicated grade (III-IV) aGVHD events. (This is a pre-determined endpoint for the 8/8 cohort and a retrospective endpoint for the 7/8 cohort).
Time Frame	First 180 days after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept	Matched Unrelated Donor - Randomized to Placebo	Mismatched Unrelated Donor - Received Abatacept	Mismatched Unrelated Donor - CIBMTR Control (No ATG)
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	CIBMTR Control cohort - Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.
Measure Participants	73	69	43	127
Number (95% Confidence Interval) [percentage of participants]	93.2 127.7%	82 118.8%	97.7 227.2%	58.7 46.2%

4. Secondary Outcome

Title	Rate of Severe (Grade III-IV) aGVHD (Based on Adjudicated aGVHD Events) up to Day +180
Description	To compare the cumulative incidence of severe (grade III-IV) aGVHD (based on adjudicated aGVHD events) up to Day 180 post-transplant between the abatacept + standard GVHD prophylaxis and standard GVHD prophylaxis regimen. (This is a pre-determined endpoint for the 8/8 cohort and a retrospective endpoint for the 7/8 cohort).
Time Frame	First 180 days after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept	Matched Unrelated Donor - Randomized to Placebo	Mismatched Unrelated Donor - Received Abatacept	Mismatched Unrelated Donor - CIBMTR Control (No ATG)
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.	CIBMTR Control cohort - Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis of calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.
Measure Participants	73	69	43	127
Number (95% Confidence Interval) [percentage of participants]	6.8 9.3%	14.8 21.4%	2.2 5.1%	32.1 25.3%

Adverse Events

Time Frame	All Serious Adverse Events (SAE) occurring through day +100 post-transplant, whether expected or unexpected, were reported. SAEs occurring after day +100 were reported only if Post-Transplant Lymphoproliferative Disorder (PTLD), fatal or unexpected.
Adverse Event Reporting Description	For the purposes of this study, PTLD, non-engraftment, graft rejection and secondary graft failure were considered SAEs regardless of their impact on the patient's condition. Adverse Events were not collected for the CIBMTR Control group (127 patients).
Arm/Group Title	Matched Unrelated Donor - Randomized to Abatacept		Matched Unrelated Donor - Randomized to Placebo		Mismatched Unrelated Donor - Received Abatacept
Arm/Group Description	A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.		A randomized, double-blind placebo-controlled cohort of patients undergoing 8/8 HLA matched unrelated donor transplant for hematologic malignancy who were randomized to standard GVHD prophylaxis and placebo (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.		Patients undergoing 7/8 HLA mismatched unrelated donor transplant for hematologic malignancy who received standard GVHD prophylaxis and abatacept (Day -1, Day +5, Day +14, Day +28 post-transplant). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.
All Cause Mortality
	Matched Unrelated Donor - Randomized to Abatacept		Matched Unrelated Donor - Randomized to Placebo		Mismatched Unrelated Donor - Received Abatacept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/73 (26%)		24/69 (34.8%)		11/43 (25.6%)
Serious Adverse Events
	Matched Unrelated Donor - Randomized to Abatacept		Matched Unrelated Donor - Randomized to Placebo		Mismatched Unrelated Donor - Received Abatacept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/73 (69.9%)		46/69 (66.7%)		30/43 (69.8%)
Blood and lymphatic system disorders
anemia	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
Bone marrow hypocellular	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
Febrile neutropenia	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
Hemolysis	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
Neutropenia	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
post-transplant lymphoproliferative disease	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
Cardiac disorders
atrial fibrilation	0/73 (0%)		1/69 (1.4%)		1/43 (2.3%)
cardiac arrest	0/73 (0%)		3/69 (4.3%)	3	0/43 (0%)	3
chest pain	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
heart failure	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
myocartial infarction	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
restrictive cardiomyopathy	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
supraventricular tachycardia	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Gastrointestinal disorders
abdominal pain	0/73 (0%)		3/69 (4.3%)	3	1/43 (2.3%)	3
Acute GVHD of the skin	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
colitis	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
diarrhea	3/73 (4.1%)	3	2/69 (2.9%)	2	0/43 (0%)	2
duodenal hemorrhage	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
enteritis	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
other - graft versus host disease	1/73 (1.4%)		2/69 (2.9%)	2	0/43 (0%)	2
Gastrointestinal GVHD	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
graft versus host disease	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
jejunal hemorrhage	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
lower gastrointestinal hemorrhage	2/73 (2.7%)	2	3/69 (4.3%)	3	0/43 (0%)	3
mucositis oral	2/73 (2.7%)	2	0/69 (0%)	2	0/43 (0%)	2
nausea	2/73 (2.7%)	2	1/69 (1.4%)	2	1/43 (2.3%)	2
pyloric ulcer	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
typhitis	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
upper gastrointestinal hemorrhage	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
General disorders
chills	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
edema limbs	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
fever	4/73 (5.5%)	8	6/69 (8.7%)	6	8/43 (18.6%)	10
infusion related reaction	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
intermittent fever	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
multi organ failure	1/73 (1.4%)		2/69 (2.9%)	2	2/43 (4.7%)	2
pain	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
infusion related reaction	1/73 (1.4%)		2/69 (2.9%)	2	1/43 (2.3%)	2
Primary disease relapse	15/73 (20.5%)	15	20/69 (29%)	20	7/43 (16.3%)	7
Hepatobiliary disorders
choledocholithiasis	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
liver graft versus host disease	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
veno-occlusive disease	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
Immune system disorders
cytokine release syndrome	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
allergic reaction	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
Infections and infestations
acute appendicitis	2/73 (2.7%)	2	0/69 (0%)	2	0/43 (0%)	2
bacteremia	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
conjunctivitis infective	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
devise infection	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
encephalitis infection	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
enterocolitis	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
enterocolitis, infectious	1/73 (1.4%)		0/69 (0%)		1/43 (2.3%)
epstein-barr virus infection reactivation	1/73 (1.4%)		0/69 (0%)		1/43 (2.3%)
eye infection	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
lung infection	1/73 (1.4%)		1/69 (1.4%)		2/43 (4.7%)	3
meningitis	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
sepsis	3/73 (4.1%)	3	6/69 (8.7%)	6	2/43 (4.7%)	2
skin infection	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
urinary tract infection	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
viral pneumonia	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
viremia	0/73 (0%)		1/69 (1.4%)		1/43 (2.3%)
Investigations
elevated creatinine	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
platelet count decreased	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
Metabolism and nutrition disorders
anorexia	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
hyponatremia	0/73 (0%)		2/69 (2.9%)	3	0/43 (0%)	3
failure to thrive	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
septic arthritis	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
myelodisplastic syndrome	1/73 (1.4%)	2	1/69 (1.4%)	2	0/43 (0%)	2
metastatic colon adenocarcinoma	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
Nervous system disorders
encephalopathy	0/73 (0%)		3/69 (4.3%)	4	0/43 (0%)	4
headache	0/73 (0%)		2/69 (2.9%)	2	0/43 (0%)	2
intracranial hemorrhage	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
reversible posterior leukoencephalopathy syndrome	2/73 (2.7%)	2	0/69 (0%)	2	1/43 (2.3%)	2
seizure	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
stroke	2/73 (2.7%)	2	1/69 (1.4%)	2	1/43 (2.3%)	2
syncope	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
transient ischemic attack	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Psychiatric disorders
altered mental status	3/73 (4.1%)	3	0/69 (0%)	3	1/43 (2.3%)	3
confusion	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
delirium	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
psychiatric disorders - altered mental status	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Renal and urinary disorders
acute kidney injury	3/73 (4.1%)	3	1/69 (1.4%)	3	1/43 (2.3%)	3
hemorrhagic cystitis	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
adult respiratory distress syndrome	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
aspiration	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
dyspnea	3/73 (4.1%)	3	0/69 (0%)	3	0/43 (0%)	3
hypoxia	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
obstrictive sleep apnea	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
pneumonitis	1/73 (1.4%)		1/69 (1.4%)		0/43 (0%)
pulmonary edema	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
respiratory failure	4/73 (5.5%)	4	4/69 (5.8%)	4	3/43 (7%)	3
Skin and subcutaneous tissue disorders
skin graft versus host disease	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
Vascular disorders
hypertension	1/73 (1.4%)		0/69 (0%)		0/43 (0%)
hematoma	0/73 (0%)		1/69 (1.4%)		0/43 (0%)
hypertension	1/73 (1.4%)		1/69 (1.4%)		1/43 (2.3%)
hypotension	2/73 (2.7%)	2	2/69 (2.9%)	2	1/43 (2.3%)	2
thromboembolic event	0/73 (0%)		0/69 (0%)		1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Matched Unrelated Donor - Randomized to Abatacept		Matched Unrelated Donor - Randomized to Placebo		Mismatched Unrelated Donor - Received Abatacept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		0/69 (0%)		0/43 (0%)

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.