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This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a haplo-identical related donor. An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's immune system
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined Bone Marrow and Kidney Transplantation | Experimental | Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belatacept | Drug | A selective T-cell (lymphocyte) costimulation blocker |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Successful Withdrawal of Immunosuppression | The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression) | 5 Years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tatsuo Kawai, MD PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
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| Label | URL |
|---|---|
| Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant. 2011 Aug;16(4):366-71. | View source |
| Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011 Jun;23(3):165-73. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Combined Bone Marrow and Kidney Transplantation | Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Combined Bone Marrow and Kidney Transplantation | Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Successful Withdrawal of Immunosuppression | The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression) | Two subjects underwent conditioning regimen | Posted | Count of Participants | Participants | No | 5 Years |
|
5 years
An adverse event is any occurrence or worsening of an undesirable or unintended sign, symptom, laboratory finding, or disease that occurs during participation in the trial.
An adverse event will be followed until it resolves or until 30 days after a participant terminates from the study, whichever comes first.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combined Bone Marrow and Kidney Transplantation | Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met. Belatacept: A selective T-cell (lymphocyte) costimulation blocker ATG: A T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation Thymic Irradiation Combined Bone Marrow/Kidney Transplantation |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombotic Microangiopathy | Renal and urinary disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HSV Lesion | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
The incidence of adverse events found around 10 days after bone marrow transplant.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tatsuo Kawai, MD PhD | Massachusetts General Hospital | 617-726-0289 | tkawai@mgh.harvard.edu |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 8, 2016 | Aug 6, 2021 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069594 | Abatacept |
| D000069283 | Rituximab |
| D014916 | Whole-Body Irradiation |
| D016030 | Kidney Transplantation |
| ID | Term |
|---|---|
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
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| ATG | Drug | A T-Cell Depleting Agent |
|
| Rituximab | Drug | B-Cell Depleting Agent |
|
| Total Body Irradiation | Radiation |
|
| Thymic Irradiation | Radiation |
|
| Combined Bone Marrow/Kidney Transplantation | Procedure |
|
| Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. | View source |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 0 |
| 2 |
| 1 |
| 2 |
| 2 |
| 2 |
| Neutropenia | Immune system disorders | Non-systematic Assessment |
|
| Heel pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
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| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D007162 | Immunoproteins |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D017582 | Renal Replacement Therapy |
| D016377 | Organ Transplantation |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D013520 | Urologic Surgical Procedures |
| D013519 | Urogenital Surgical Procedures |