Trial Outcomes & Findings for BMT and High Dose Post-Transplant Cyclophosphamide for Chimerism Induction and Renal Allograft Tolerance (NCT NCT02029638)

NCT ID: NCT02029638

Last Updated: 2018-09-24

Results Overview

Operational tolerance is defined as remaining off all immunosuppression 52 weeks after completion of immunosuppression withdrawal, with no evidence of biopsy-proven allograft rejection and, with acceptable renal function defined as a serum creatinine that has increased no more than 25% above baseline at the primary endpoint visit. Baseline creatinine is defined as the average of the lowest three creatinine values during 2 to 4 weeks post-transplant, excluding days on dialysis. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 4 participants
• Primary outcome timeframe: Transplantation through 52 Weeks after Discontinuation of All Immunosuppression
• Results posted on: 2018-09-24

Participant Flow

Participant milestones

Measure	Enrolled, Screen Failure Participants were consented and enrolled in the study, but did not receive a full evaluation of all criteria for study participation. These participants were terminated during the screening process due to a decision by study sponsor	Enrolled, Not Transplanted Participants were consented and enrolled in the study, fulfilling all criteria for study participation. The participants initiated protocol specified pre-transplant treatment, but did not receive a renal transplantation followed by bone marrow infusion, per protocol.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Overall Study STARTED	2	1	1
Overall Study COMPLETED	0	1	0
Overall Study NOT COMPLETED	2	0	1

Reasons for withdrawal

Measure	Enrolled, Screen Failure Participants were consented and enrolled in the study, but did not receive a full evaluation of all criteria for study participation. These participants were terminated during the screening process due to a decision by study sponsor	Enrolled, Not Transplanted Participants were consented and enrolled in the study, fulfilling all criteria for study participation. The participants initiated protocol specified pre-transplant treatment, but did not receive a renal transplantation followed by bone marrow infusion, per protocol.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Overall Study Death	0	0	1
Overall Study Decision by Study Sponsor or Regulatory	2	0	0

Baseline Characteristics

BMT and High Dose Post-Transplant Cyclophosphamide for Chimerism Induction and Renal Allograft Tolerance

Baseline characteristics by cohort

Measure	Enrolled, Screen Failure n=2 Participants Participants were consented and enrolled in the study, but did not receive a full evaluation of all criteria for study participation. These participants were terminated during the screening process due to a decision by study sponsor.	Enrolled, Not Transplanted n=1 Participants Participants were consented and enrolled in the study, fulfilling all criteria for study participation. The participants initiated protocol specified pre-transplant treatment, but did not receive a renal transplantation followed by bone marrow infusion, per protocol.	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Serum Creatinine	NA mg/dL STANDARD_DEVIATION NA • n=5 Participants	NA mg/dL STANDARD_DEVIATION NA • n=7 Participants	2.1 mg/dL STANDARD_DEVIATION NA • n=5 Participants	2.1 mg/dL STANDARD_DEVIATION NA • n=4 Participants

PRIMARY outcome

Timeframe: Transplantation through 52 Weeks after Discontinuation of All Immunosuppression

Population: Transplanted Per Protocol Participants

Operational tolerance is defined as remaining off all immunosuppression 52 weeks after completion of immunosuppression withdrawal, with no evidence of biopsy-proven allograft rejection and, with acceptable renal function defined as a serum creatinine that has increased no more than 25% above baseline at the primary endpoint visit. Baseline creatinine is defined as the average of the lowest three creatinine values during 2 to 4 weeks post-transplant, excluding days on dialysis. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Percent of Participants Who Achieved Operational Tolerance	0 Percent of participants Interval 0.0 to 97.5	—

SECONDARY outcome

Timeframe: Transplant to Two Years Post-Transplant

Population: Transplanted Per Protocol Participants

Graft-versus-host disease (GVHD) is a medical complication that can occur after a person receives transplanted tissue, most commonly occurring after a bone marrow transplant. The white blood cells from the donated tissue recognize the tissue recipient's cells as foreign. These donor cells then attack the recipient's cells.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Participants Experiencing an Incidence of Graft-versus-Host Disease Post-Transplant	1 Participants	—

SECONDARY outcome

Timeframe: Transplant to Two Years Post-Transplant

Population: Transplanted Per Protocol Participants

Graft-versus-host disease (GVHD) is a medical complication that can occur after a person receives transplanted tissue, most commonly occurring after a bone marrow transplant. The white blood cells from the donated tissue recognize the tissue recipient's cells as foreign. These donor cells then attack the recipient's cells. Severity of GVHD is based on skin, liver, and intestinal tract symptoms, ranging from I to IV, with IV being the worst. This measure counts the number of participants experiencing GVHD by severity.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Severity of Graft-versus-Host Disease in Transplanted Participants Grade I	1 Participants	—
Severity of Graft-versus-Host Disease in Transplanted Participants Grade II	0 Participants	—
Severity of Graft-versus-Host Disease in Transplanted Participants Grade III	0 Participants	—
Severity of Graft-versus-Host Disease in Transplanted Participants Grade IV	0 Participants	—

SECONDARY outcome

Timeframe: Transplant to Two Years Post-Transplant

Population: Transplanted Per Protocol Participants

Graft-versus-host disease (GVHD) is a medical complication that can occur after a person receives transplanted tissue, most commonly occurring after a bone marrow transplant. The white blood cells from the donated tissue recognize the tissue recipient's cells as foreign. These donor cells then attack the recipient's cells. Duration (in days) is measured as the time from the start of the GVHD event to the end of the GVHD event.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Duration in Days of Graft-versus-Host Disease in Transplanted Participants	7 Days Standard Deviation NA Standard deviation cannot be calculated for one participant.	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants

Engraftment syndrome is a complication that can occur following bone marrow transplant. The presence of engraftment syndrome is diagnosed by monitoring the common symptoms, which include: fever, rash, fluid in the lungs, and serum creatinine values above 4 mg/dL occurring within a week of absolute neutrophil recovery (e.g., first day after three consecutive daily absolute neutrophil counts ≥ 500 per µL), without apparent other cause.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants With Engraftment Syndrome	0 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: No statistical analyses provided for 'Duration of Engraftment Syndrome in Transplanted Participants' because no participants in the Per Protocol population experienced engraftment syndrome.

Engraftment syndrome is a complication that can occur following bone marrow transplant. The presence of engraftment syndrome is diagnosed by monitoring the common symptoms, which include: fever, rash, fluid in the lungs, and serum creatinine values above 4 mg/dL occurring within a week of absolute neutrophil recovery (e.g., first day after three consecutive daily absolute neutrophil count ≥ 500 per µL), without apparent other cause. Duration (in days) is measured as the time from the start of the engraftment syndrome event to the end of the engraftment syndrome event.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants

Number of participant deaths after receiving a transplant per protocol.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants Who Died	1 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants

Acute renal allograft rejection demonstrated either by biopsy or clinically (when a biopsy could not be performed). This measure includes participants with biopsy proven acute renal allograft rejection and those that have creatinine values 25% or greater relative to baseline for over 72 hours. Baseline serum creatinine is defined as the average of the lowest three serum creatinine values during 2 to 4 weeks post-transplant, excluding days on dialysis.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants With Acute Renal Allograft Rejection	1 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants

This outcome includes results from biopsies with proven acute renal allograft rejection according to the 2007 Banff Classification Renal Allograft Pathology. A Banff result of indeterminate is not classified as rejection.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Cellular Rejection Banff Grade IA	0 participants	—
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Cellular Rejection Banff Grade IB	0 participants	—
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Cellular Rejection Banff Grade IIA	0 participants	—
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Cellular Rejection Banff Grade IIB	0 participants	—
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Cellular Rejection Banff Grade III	0 participants	—
Histological Severity of Biopsies Demonstrating Acute Rejection as Defined by Banff 2007 Classification Renal Allograft Pathology Acute Antibody Mediated Rejection	0 participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants

Outcome includes participants who experienced chronic T cell-mediated rejection, antibody-mediated rejection and progressive interstitial fibrosis/tubular atrophy (IF/TA), transplant glomerulopathy or chronic obliterative arteriopathy, without an alternative, non-rejection related cause. Reference: Banff 2007 Classification Renal Allograft Pathology definition of terms.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants With Chronic T Cell-Mediated or Antibody-Mediated Rejection	1 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months After Enrollment)

Population: Transplanted Per Protocol Participants who experienced acute rejection.

Number of days post-transplant to the first episode of acute rejection that required treatment. This includes acute rejection episodes requiring treatment that were not biopsy proven.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Days Post-Transplant to the First Episode of Acute Rejection Requiring Treatment	23 Days Standard Deviation NA Standard deviation cannot be calculated for one participant.	—

SECONDARY outcome

Timeframe: First Dose of Study Medication to End of Study (Up to 25 Months After Enrollment)

Population: Safety population, which includes all participants who received any study medication.

AEs reported as an infection, wound complication, post-transplant diabetes, hemorrhagic cystitis and/or malignancy.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy Infection	0 Events	2 Events
Number of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy Wound complications	0 Events	0 Events
Number of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy Post-transplant diabetes	0 Events	0 Events
Number of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy Hemorrhagic cystitis	0 Events	0 Events
Number of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy Malignancy	0 Events	0 Events

SECONDARY outcome

Timeframe: First Dose of Study Medication to End of Study (Up to 25 Months After Enrollment)

Population: Safety population, which includes all participants who received any study medication.

AEs reported as an infection, wound complication, post-transplant diabetes, hemorrhagic cystitis and/or malignancy. Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 4.0.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Adverse Events (AEs) by Severity- Including Infection, Wound Complications, Post-Transplant Diabetes, Hemorrhagic Cystitis and Malignancy Grade 1	0 Events	0 Events
Number of Adverse Events (AEs) by Severity- Including Infection, Wound Complications, Post-Transplant Diabetes, Hemorrhagic Cystitis and Malignancy Grade 2	0 Events	0 Events
Number of Adverse Events (AEs) by Severity- Including Infection, Wound Complications, Post-Transplant Diabetes, Hemorrhagic Cystitis and Malignancy Grade 3	0 Events	2 Events
Number of Adverse Events (AEs) by Severity- Including Infection, Wound Complications, Post-Transplant Diabetes, Hemorrhagic Cystitis and Malignancy Grade 4	0 Events	0 Events
Number of Adverse Events (AEs) by Severity- Including Infection, Wound Complications, Post-Transplant Diabetes, Hemorrhagic Cystitis and Malignancy Grade 5	0 Events	0 Events

SECONDARY outcome

Timeframe: First Dose of Study Medication to End of Study (Up to 25 Months After Enrollment)

Population: Participants who received any study medication and experienced at least one AE inclusive of infection, wound complications, post-transplant diabetes, hemorrhagic cystitis and/or malignancy.

AEs reported as an infection, wound complication, post-transplant diabetes, hemorrhagic cystitis and/or malignancy. Time (in days) from the start date of the AE until the end date of the AE. Two events contributed to this calculation.

Outcome measures

Measure	Enrolled, Transplanted Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Duration in Days of Adverse Events (AEs)- Including Infection, Wound Complications, Post-transplant Diabetes, Hemorrhagic Cystitis and Malignancy	—	9.5 Days Standard Deviation 2.12

SECONDARY outcome

Timeframe: Initiation of Immunosuppression Withdrawal to End of Study (to 25 months)

Population: Transplanted Per Protocol Participants

Donor-specific antibodies are directed against antigens expressed on donor organs. These antibodies can result in an immune attack on the transplanted organ, increasing risk of graft loss and/or rejection.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants Who Developed Donor- Specific Antibody After Initiation of Immunosuppression Withdrawal	0 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 months)

Population: Transplanted Per Protocol Participants

Donor-specific antibodies are directed against antigens expressed on donor organs. These antibodies can result in an immune attack on the transplanted organ, increasing risk of graft loss and/or rejection.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants Who Developed Donor-Specific Antibody During Study Participation	0 Participants	—

SECONDARY outcome

Timeframe: Post-Transplant Neutrophil Nadir to Neutrophil Recover

Population: Transplanted Per Protocol Participants

Time (in days) from neutrophil nadir, the first day post-transplant on which the absolute neutrophil count (ANC) is below 500 per µL, to the first day after three consecutive daily ANCs ≥ 500 per µL. ANC is a measure of the number of neutrophils present in the blood. Neutrophils are a type of white blood cell that fight against infection. A healthy person has an ANC between 2,500 and 6,000 per µL. A value below 500 per µL means the risk of infection is higher.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Days From Neutrophil Nadir to Absolute Neutrophil Recovery	15 Days Standard Deviation NA Standard deviation cannot be calculated for one participant.	—

SECONDARY outcome

Timeframe: Transplant to Platelet Count Recovery

Population: Transplanted Per Protocol Participants

Time (in days) from transplant to the first day of a platelet count of ≥20,000 per μL without a prior platelet transfusion in the preceding seven days. Low platelet numbers is associated with increased risk of bleeding and bruising. A healthy person has a platelet count ranging from 150,000 to 450,000 platelets per microliter of blood.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Days From Transplant to Platelet Count Recovery	36 Days Standard Deviation NA Standard deviation cannot be calculated for one participant.	—

SECONDARY outcome

Timeframe: Transplant to 52 Weeks after Discontinuation of All Immunosuppression

Population: Transplanted Per Protocol Participants

Number of transplanted participants who remained off immunosuppression for ≥52 weeks, including those in whom the 52 week biopsy was not performed. This outcome included participants who were able to withdrawal successfully from all immunosuppression medication and remain off all immunosuppression for 52 weeks after the completion of withdrawal.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Transplanted Participants Who Remained Off Immunosuppression for at Least 52 Weeks, Including Those in Whom the 52 Week Biopsy Was Not Performed	0 Participants	—

SECONDARY outcome

Timeframe: Transplant to End of Study (Up to 25 Months)

Population: Transplanted Per Protocol Participants

Participants who were able to withdrawal successfully from all immunosuppression medication and remained off all immunosuppression medication for the remainder of the study.

Outcome measures

Measure	Enrolled, Transplanted n=1 Participants Participants were consented, enrolled, and fulfilled all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.	Enrolled, Transplanted Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Number of Participants Free From Return to Immunosuppression for the Duration of the Study	0 Participants	—

Adverse Events

Enrolled, Not Transplanted

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Enrolled, Transplanted

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Measure	Enrolled, Not Transplanted n=1 participants at risk Participants were consented and enrolled in the study, but did not receive a full evaluation of all criteria for study participation. These participants were terminated during the screening process due to a decision by study sponsor.	Enrolled, Transplanted n=1 participants at risk Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Nervous system disorders Benign intracranial hypertension	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)
Infections and infestations Infection	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)
Infections and infestations Sinusitis	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)
Vascular disorders Shock haemorrhagic	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)
Injury, poisoning and procedural complications Tibia fracture	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)

Other adverse events

Measure	Enrolled, Not Transplanted n=1 participants at risk Participants were consented and enrolled in the study, but did not receive a full evaluation of all criteria for study participation. These participants were terminated during the screening process due to a decision by study sponsor.	Enrolled, Transplanted n=1 participants at risk Participants were consented, enrolled, fulfilling all study criteria. Participants received three .5, 2, and 2 mg/kg doses of ATG (7-9 days before transplant) pre-medicated with 650 mg acetaminophen, 25 mg diphenhydramine and steroid taper of methylprednisolone, five 30 mg/m\^2/day doses of fludarabine (2-6 days before transplant), and two 14.5 mg/kg/day doses of low-dose cyclophosphamide (5-6 days before transplant), along with total body irradiation the day before transplant. Participants received a living renal transplant followed by bone marrow infusion. Two 50 mg/kg/day doses of high-dose cyclophosphamide were given days 3 and 4 post-transplant with MESNA. Filgrastim was given starting on day 5 post-transplant until absolute neutrophil recovery. Standard immunosuppression of tacrolimus, MMF, and prednisone began on day 5 post-transplant and given for at least 26 weeks post-transplant. Eligible participants were gradually withdrawn from medication over a period of 24-40 weeks.
Investigations Blood creatinine increased	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)
Immune system disorders Acute graft versus host disease in skin	0.00% 0/1 • First study medication dosing through end of study (up to 25 months after enrollment)	100.0% 1/1 • Number of events 1 • First study medication dosing through end of study (up to 25 months after enrollment)

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place