Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00801632
• Collaborator: Immune Tolerance Network (ITN) (Other)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 71
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation; Kidney Failure, Chronic	Procedure: Kidney Transplantation; Procedure: Bone marrow transplantation; Biological: MEDI-507; Drug: cyclophosphamide; Biological: rituximab; Drug: Tacrolimus; Drug: corticosteroids; Radiation: thymic irradiation	Phase 2

Detailed Description

All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.

Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.

Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.

Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.

Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Renal Allograft Tolerance Through Mixed Chimerism
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Kidney and Marrow Recipients Combined kidney and bone marrow transplant

Procedure: Kidney Transplantation; Surgical transplantation of donor kidney; Other Names: Renal Transplantation ; Procedure: Bone marrow transplantation; During kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone; Biological: MEDI-507; 0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1; Other Names: siplizumab anti-CD2 monoclonal antibody ; Drug: cyclophosphamide; 60 mg/kg infusion on days -5, -4; Other Names: Cytoxan ; Biological: rituximab; 375 mg/m^2 infusion on days -7, -2, 5, and 12; Other Names: Rituxan ; Drug: Tacrolimus; 0.05 mg/kg intravenously twice daily starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56; Other Names: PROGRAF® ; Drug: corticosteroids; 2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20; Other Names: methylprednisolone prednisone ; Radiation: thymic irradiation; 700 cGy of thymic irradiation administered in a single dose on day -1

Outcome Measures

Primary Outcome Measures

1. Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks [48 months post-transplant]

   A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.

Secondary Outcome Measures

1. Percentage of Participants Experiencing Acute Rejection [Transplantation until study completion or participant termination (up to five years)]

   The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.

2. Change in Renal Function [Transplantation until study completion or participant termination (up to five years)]

   Change in renal function as seen in serum creatinine values from baseline until study completion or participant termination. Baseline is defined as the lowest serum creatinine collected during stabilization period or in the four weeks following the end of the stabilization period. The stabilization period is defined as four consecutive creatinine values close in value (not differing more than 0.3 mg/dL). Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.

3. Percentage of Participants With Graft Survival Through 156 Weeks [Transplantation until week 156]

   The percentage of participants with graft survival from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded. Graft survival is defined as the time to week 156 or graft loss. Graft loss is defined as the day on which a graft is deemed irreversibly nonfunctional and dialysis is begun, a transplantectomy is performed, or the participant is re-transplanted, whichever comes first. Six consecutive weeks of dialysis are required for the diagnosis of graft loss, though the date of graft loss will be defined as the date of first dialysis.

4. Percentage of Participants Surviving Through 156 Weeks [Transplantation until week 156]

   The percentage of participants who survived from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded.

5. Time to Neutrophil Recovery Following Transplant [Transplantation until study completion or participant termination (participants followed up to five years)]

   Time (in days) until neutrophil recovery following transplant. Neutrophil recovery is defined as an absolute neutrophil count (ANC) > 500/mm^3 at three consecutive assessments on different days post-transplant. Time to recovery is time from transplantation until the first assessment date used to confirm the recovery.

6. Time to Platelet Recovery Following Transplant [Transplantation until study completion or participant termination (participants followed up to five years)]

   Time (in days) until platelet recovery following transplant. Platelet recovery is defined as a platelet count >20,000 /mm^3 and where no transfusion is required. Time to recovery is time from transplantation until platelet value recovers.

7. Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection [Transplantation until study completion or participant termination (participants followed up to five years)]

   Clinically significant invasive or resistant opportunistic infections include cytomegalovirus, herpes zoster, and candida.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Awaiting first or second transplant with a living donor or first transplant with a cadaveric donor

• For living-donor transplants, must have one or more HLA antigen-mismatched donors identified

• Serologic evidence of prior exposure to Epstein-Barr virus (EBV)

Exclusion Criteria:

• ABO blood group-incompatibility for a kidney graft of tissue from a donor

• Decreased circulating white blood cell count

• Positive for HIV-1, hepatitis B and C viruses

• Have had prior radiation therapy that could limit dose

• Lung capacity <50% of predicted normal

• Evidence of insufficient cardiac capacity

• Unwilling to use adequate contraception until 2 years after transplant

• Lactation or pregnancy

• Presence of antibody against the donor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Immune Tolerance Network (ITN)

Investigators

• Principal Investigator: David Sachs, MD, Massacusetts General Hospital
• Principal Investigator: Ben Cosimi, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Immune Tolerance Network

Publications

• Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00801632
• Other Study ID Numbers: DAIT ITN036ST
• First Posted: Dec 3, 2008
• Last Update Posted: Nov 10, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): renal allograft tolerance; mixed chimerism; kidney transplant; bone marrow transplant; antirejection; immunosuppression
• Additional relevant MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Prednisone; Methylprednisolone; Cyclophosphamide; Rituximab; Tacrolimus

Study Results

Participant Flow

Recruitment Details	Participants with end-stage renal disease and no evidence of prior sensitization were enrolled between December 2008 and September 2009.

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.8 (8.6)
Sex: Female, Male (Count of Participants)
Female	3 60%
Male	2 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	5 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%
Baseline Creatinine Level (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.9 (1.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks
Description	A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.
Time Frame	48 months post-transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Number [participants]	3 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MEDI-507
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	60.0
	Confidence Interval	(2-Sided) 95%; 14.7 to 94.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Clopper-Pearson used to derive confidence interval

2. Secondary Outcome

Title	Percentage of Participants Experiencing Acute Rejection
Description	The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Time Frame	Transplantation until study completion or participant termination (up to five years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Number (95% Confidence Interval) [Percentage of Participants]	40 800%

3. Secondary Outcome

Title	Change in Renal Function
Description	Change in renal function as seen in serum creatinine values from baseline until study completion or participant termination. Baseline is defined as the lowest serum creatinine collected during stabilization period or in the four weeks following the end of the stabilization period. The stabilization period is defined as four consecutive creatinine values close in value (not differing more than 0.3 mg/dL). Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.
Time Frame	Transplantation until study completion or participant termination (up to five years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Baseline Serum Creatinine	1.9 (1.2)
Study Termination/Completion	3.2 (2.7)
Change from Baseline	1.2 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MEDI-507
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.215
	Comments	P-value based on a paired t-test comparing baseline creatinine level with the level at study completion/participant termination.
	Method	t-test, 2 sided
	Comments	The test describes whether the average of the difference is different from zero.

4. Secondary Outcome

Title	Percentage of Participants With Graft Survival Through 156 Weeks
Description	The percentage of participants with graft survival from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded. Graft survival is defined as the time to week 156 or graft loss. Graft loss is defined as the day on which a graft is deemed irreversibly nonfunctional and dialysis is begun, a transplantectomy is performed, or the participant is re-transplanted, whichever comes first. Six consecutive weeks of dialysis are required for the diagnosis of graft loss, though the date of graft loss will be defined as the date of first dialysis.
Time Frame	Transplantation until week 156

Outcome Measure Data

Analysis Population Description

Participants who were followed at least three years after transplantation or experienced graft loss prior to week 156

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Number (95% Confidence Interval) [Percentage of Participants]	80 1600%

5. Secondary Outcome

Title	Percentage of Participants Surviving Through 156 Weeks
Description	The percentage of participants who survived from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded.
Time Frame	Transplantation until week 156

Outcome Measure Data

Analysis Population Description

Participants who were followed at least three years after transplantation or experienced death prior to week 156

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	4
Number (95% Confidence Interval) [Percentage of Participants]	100 2000%

6. Secondary Outcome

Title	Time to Neutrophil Recovery Following Transplant
Description	Time (in days) until neutrophil recovery following transplant. Neutrophil recovery is defined as an absolute neutrophil count (ANC) > 500/mm^3 at three consecutive assessments on different days post-transplant. Time to recovery is time from transplantation until the first assessment date used to confirm the recovery.
Time Frame	Transplantation until study completion or participant termination (participants followed up to five years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Mean (Standard Deviation) [days]	14.0 (4.1)

7. Secondary Outcome

Title	Time to Platelet Recovery Following Transplant
Description	Time (in days) until platelet recovery following transplant. Platelet recovery is defined as a platelet count >20,000 /mm^3 and where no transfusion is required. Time to recovery is time from transplantation until platelet value recovers.
Time Frame	Transplantation until study completion or participant termination (participants followed up to five years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Mean (Standard Deviation) [days]	1.0 (0.0)

8. Secondary Outcome

Title	Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection
Description	Clinically significant invasive or resistant opportunistic infections include cytomegalovirus, herpes zoster, and candida.
Time Frame	Transplantation until study completion or participant termination (participants followed up to five years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
Measure Participants	5
Number (95% Confidence Interval) [Percentage of Participants]	0 0%

Adverse Events

Time Frame	Transplantation until study completion or participant termination (up to five years)
Arm/Group Title	MEDI-507
Arm/Group Description	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.
All Cause Mortality
	MEDI-507
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MEDI-507
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)	1
Thrombotic microangiopathy	1/5 (20%)	1
Cardiac disorders
Atrial fibrillation	1/5 (20%)	1
Gastrointestinal disorders
Stomatitis	1/5 (20%)	1
Immune system disorders
Engraftment syndrome	5/5 (100%)	5
Transplant rejection	2/5 (40%)	2
Infections and infestations
Gastroenteritis	1/5 (20%)	1
Urinary tract infection	1/5 (20%)	1
Viral infection	1/5 (20%)	1
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/5 (20%)	1
Investigations
Blood creatinine increased	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/5 (20%)	1
Vascular disorders
Haematoma	1/5 (20%)	1
Thrombosis	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	MEDI-507
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anaemia	2/5 (40%)	2
Neutropenia	1/5 (20%)	6
Thrombocytopenia	3/5 (60%)	3
Gastrointestinal disorders
Diarrhoea	1/5 (20%)	1
Gastritis	1/5 (20%)	1
Nausea	1/5 (20%)	1
Vomiting	1/5 (20%)	1
General disorders
Catheter related complication	1/5 (20%)	1
Pyrexia	1/5 (20%)	1
Infections and infestations
Catheter site infection	1/5 (20%)	1
Clostridium difficile colitis	2/5 (40%)	2
Urinary tract infection	3/5 (60%)	4
Injury, poisoning and procedural complications
Drug toxicity	1/5 (20%)	1
Limb injury	1/5 (20%)	1
Investigations
Alanine aminotransferase increased	2/5 (40%)	2
Weight increased	2/5 (40%)	2
Metabolism and nutrition disorders
Hyperglycaemia	1/5 (20%)	1
Hyperkalaemia	1/5 (20%)	1
Hyponatraemia	1/5 (20%)	1
Hypophosphataemia	2/5 (40%)	2
Renal and urinary disorders
Proteinuria	4/5 (80%)	4
Renal failure acute	1/5 (20%)	1

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.