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This study is being conducted to determine how safe and effective using an immune cell (b cell) depleting therapy and/or Thymoglobulin is in patients with a kidney transplant who are experiencing certain types of rejection.
The purpose of the study is to determine safety and efficacy of treatment if mixed (cellular and antibody) mediated acute rejection with addition of B-cell depleting therapy to Thymoglobulin in kidney and simultaneous kidney pancreas allograft recipients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rabbit Antithymocyte Globulin (RATG) | Active Comparator | Rabbit Antithymocyte Globulin (RATG) All patients will receive RATG (Thymoglobulin) dosed based on CD3 count. Patients will be redosed when the cluster of differentiation 3 (CD3) count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. 1.5mg/kg/day over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels > 25 cells/mm3); Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose. |
|
| RATG/Rituximab | Experimental | Rabbit Antithymocyte Globulin (RATG) + Rituximab Subjects will be given 1.5mg/kg/day of RATG over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels > 25 cells/mm3); Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose. |
|
| RATG/Bortezomib |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rabbit Antithymocyte Globulin (RATG) | Drug | All patients will receive Thymoglobulin dosed based on CD3 count. Patients will be redosed when the CD3 count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients in Each Group With Any of the Following: Rejection Reversal or Recurrent Rejection | Rejection Reversal is a return of serum creatinine to within 115% of the baseline value, or histologic reversal occurring within 14 days of initiation of treatment. Recurrent Rejection is histologic evidence of rejection noted on a biopsy specimen obtained up to 3 months after documented rejection reversal. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Allografts With C4d Focal Positive Pretreatment Biopsy | Day 1 | |
| Renal Allograft Survival | 1 year after rejection treatment | |
| Mean Serum Creatinine |
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Inclusion Criteria
Each subject must meet all of the following inclusion criteria to be enrolled in the study:
Exclusion Criteria
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
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| Name | Affiliation | Role |
|---|---|---|
| E. Steve Woodle, MD | University of Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Christ Hospital | Cincinnati | Ohio | 45202 | United States | ||
| University of Cincinnati Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rabbit Antithymocyte Globulin (RATG) | RATG Rabbit Antithymocyte Globulin (RATG): All patients will receive Thymoglobulin dosed based on cluster of differentiation 3 (CD3) count. Patients will be redosed when the CD3 count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Bortezomib: Patient will receive 1.3 mg/m2 via intravenous push (IVP) over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
| FG001 | RATG/Rituximab | Rabbit Antithymocyte Globulin (RATG) + Rituximab Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. |
| FG002 | RATG/Bortezomib | Rabbit Antithymocyte Globulin (RATG) + Bortezomib Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rabbit Antithymocyte Globulin (RATG) | RATG Rabbit Antithymocyte Globulin (RATG): All patients will receive Thymoglobulin dosed based on CD3 count. Patients will be redosed when the CD3 count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Patients in Each Group With Any of the Following: Rejection Reversal or Recurrent Rejection | Rejection Reversal is a return of serum creatinine to within 115% of the baseline value, or histologic reversal occurring within 14 days of initiation of treatment. Recurrent Rejection is histologic evidence of rejection noted on a biopsy specimen obtained up to 3 months after documented rejection reversal. | Posted | Number | participants | 1 year |
|
1 year
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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 | Rabbit Antithymocyte Globulin (RATG) | RATG Rabbit Antithymocyte Globulin (RATG): All patients will receive Thymoglobulin dosed based on CD3 count. Patients will be redosed when the CD3 count is ≥ 25. Depending on rejection severity, Thymoglobulin will be given for a maximum of 7-14 days. CD3 levels will be monitored daily. Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death due to hypoglycemic attack and respiratory distress | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 4 Thrombocytopenia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| E. Steve Woodle, MD | University of Cincinnati | 513-558-6001 | woodlees@ucmail.uc.edu |
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| ID | Term |
|---|---|
| C512542 | thymoglobulin |
| D000069283 | Rituximab |
| D000069286 | Bortezomib |
| D000082 | Acetaminophen |
| D006633 | Histamine Antagonists |
| D004155 | Diphenhydramine |
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Rabbit Antithymocyte Globulin (RATG) + Bortezomib -Subjects will be given 1.5mg/kg/day of RATG over 6 hrs with 1st dose (D1) and over 4 hours for each dose thereafter. (day 1 then when CD3 levels > 25 cells/mm3). Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. Bortezomib will be given at a dose of 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Methylprednisolone will be administered prior to each bortezomib dose. On days 2 and 5, administer methylprednisolone 100 mg intravenous push (IVP). On days 9 and 12, administer methylprednisolone 50 mg intravenous push (IVP). If thymoglobulin is administered the same day as bortezomib, the order of administration is- methylprednisolone, then bortezomib, then thymoglobulin. |
|
|
|
| Rituximab | Drug | Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. |
|
|
| Bortezomib | Drug | Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
|
|
| Acetaminophen | Drug | Patients will be premedicated with acetaminophen prior to dosing per institution standard of care. |
|
|
| Antihistamine | Drug | Patients will be premedicated with an antihistamine prior to dosing per institution standard of care. |
|
|
| Methylprednisolone | Drug | Methylprednisolone 250 mg with 1st dose of Thymoglobulin. Methylprednisolone 125 mg on treatment day 2 subsequent corticosteroids per institution standard of care; following treatment, corticosteroid therapy will resume at the pre-rejection dose. |
|
|
Renal allograft function as determined by change (∆) in Calculated creatinine clearance by Cockcroft-Gault at 7, 14, 28, 60, and 90 days and 1 year post therapy initiation |
| 7, 14, 28, 60, 90 days and 1 year post therapy initiation |
| Incidence of Death | 90 days |
| Number of Patients With Allografts With C4d Diffuse Positive Pretreatment Biopsy | 90 days |
| Incidence of Post Transplant Lymphoproliferative Disorder (PTLD) | 1 year |
| Cincinnati |
| Ohio |
| 45267 |
| United States |
| BG001 | RATG/Rituximab | Rabbit Antithymocyte Globulin (RATG) + Rituximab Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. |
| BG002 | RATG/Bortezomib | Rabbit Antithymocyte Globulin (RATG) + Bortezomib Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Type of Transplant | Number | participants |
|
| OG001 | RATG/Rituximab | Rabbit Antithymocyte Globulin (RATG) + Rituximab Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. |
| OG002 | RATG/Bortezomib | Rabbit Antithymocyte Globulin (RATG) + Bortezomib Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. |
|
|
| Secondary | Number of Patients With Allografts With C4d Focal Positive Pretreatment Biopsy | Posted | Number | participants | Day 1 |
|
|
|
| Secondary | Renal Allograft Survival | Posted | Number | participants | 1 year after rejection treatment |
|
|
|
| Secondary | Mean Serum Creatinine | Renal allograft function as determined by change (∆) in Calculated creatinine clearance by Cockcroft-Gault at 7, 14, 28, 60, and 90 days and 1 year post therapy initiation | Posted | Mean | Standard Deviation | mg/dL | 7, 14, 28, 60, 90 days and 1 year post therapy initiation |
|
|
|
| Secondary | Incidence of Death | Posted | Number | participants | 90 days |
|
|
|
| Secondary | Number of Patients With Allografts With C4d Diffuse Positive Pretreatment Biopsy | Posted | Number | participants | 90 days |
|
|
|
| Secondary | Incidence of Post Transplant Lymphoproliferative Disorder (PTLD) | Posted | Number | participants | 1 year |
|
|
|
| 7 |
| 10 |
| 10 |
| 10 |
| EG001 | RATG/Rituximab | Rabbit Antithymocyte Globulin (RATG) + Rituximab Rituximab: Rituximab dose of 375 mg/ m2 on day 2. Patients will be premedicated with an antihistamine and acetaminophen prior to dosing per institution standard of care. | 5 | 9 | 9 | 9 |
| EG002 | RATG/Bortezomib | Rabbit Antithymocyte Globulin (RATG) + Bortezomib Bortezomib: Patient will receive 1.3 mg/m2 via IV push over 3-5 seconds on days 2, 5, 9, and 12. Consolidation course of bortezomib will be dosed at 1.3 mg/m2 IVP X 4 doses administered on days 1, 4, 7 and 10. | 7 | 10 | 7 | 10 |
| Pain and Tenderness at Pheresis Line | General disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Coronary Artery Disease | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Surgical Complication | Surgical and medical procedures | CTCAE (3.0) | Systematic Assessment |
|
| Gastrointestinal Disorder | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Renal Dysfunction | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Serum Sickness | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thombosis | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage of Lower GI | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Grade 1 Nausea/Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Grade 2 Nausea/Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Grade 1 Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Worsened Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Grade 2 Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 4 Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Cytomegalovirus (CMV) infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| BK Virus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Productive Cough | General disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Tingling | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Level 1 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Level 2 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Level 3 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 2 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Level 4 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Level 5 Peripheral Neuropathy | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D018494 | Histamine Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D005021 | Ethylamines |
| D001559 | Benzhydryl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
|
| 28 days |
|
| 60 days |
|
| 90 days |
|
| 1 year |
|