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| ID | Type | Description | Link |
|---|---|---|---|
| IRB 106591 |
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The purpose of this research is to compare the effectiveness of Tacrolimus and Rapamycin to Tacrolimus and Methotrexate in the prevention of severe graft-versus-host-disease. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). An allogeneic hematopoietic cell transplant is a transplant using bone marrow and blood cells that come from someone other than the patient (a donor).
All drugs used in this study have been used in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Methotrexate used in combination are currently used as standard of care in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Rapamycin is a newer combination we are testing to see if it would be better than Tacrolimus and Methotrexate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus / Rapamycin (TAC/RAPA) | Active Comparator | Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Rapamycin: given the day before transplant and continued daily for at least one year. |
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| Tacrolimus / Methotrexate (TAC/MTX) | Active Comparator | Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus (TAC) | Drug | Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant | Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme. Acute GVHD classified as the following:
| 100 Days Post Transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) | Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employed to test differences in percent Treg (% Treg/total CD4+ cells). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Claudio Anasetti, MD | HLeeMoffittCancerCenter | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H.Lee Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22689677 | Derived | Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-9. doi: 10.3324/haematol.2012.067140. Epub 2012 Jun 11. |
| Label | URL |
|---|---|
| H.Lee Moffitt Cancer Center \& Research Institute | View source |
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Patients recruited between 09/10/2008 through 05/13/2011 from the Blood and Marrow Transplant Program patient population.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 Tacrolimus / Rapamycin | Tacrolimus / Rapamycin Tacrolimus and Rapamycin (Sirolimus): Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Methotrexate (MTX) | Drug | Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance. |
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| Rapamycin (RAPA) | Drug | Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily. |
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| 30 days and 90 days |
| 2 Year Post Transplant Overall Survival (OS) Rate | Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause . | 2 years |
| 2 Tacrolimus / Methotrexate |
Tacrolimus / Methotrexate Tacrolimus and Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance. |
| COMPLETED |
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| NOT COMPLETED |
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Based on our preliminary data collected from patients receiving TAC/MTX, the acute GVHD (aGVHD) rate is estimated to be 80% at 100 days. A two-sided log-rank test will achieve 90% power at a 0.1 significance level. The result of this calculation serves as an approximation of power/sample size for the test we propose to use for the primary endpoint.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tacrolimus / Rapamycin | Tacrolimus / Rapamycin Tacrolimus / Rapamycin: Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily. |
| BG001 | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate Tacrolimus / Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant | Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme. Acute GVHD classified as the following:
| All participants who received treatment | Posted | Number | 95% Confidence Interval | percentage of participants | 100 Days Post Transplant |
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| Secondary | Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) | Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employed to test differences in percent Treg (% Treg/total CD4+ cells). | Posted | Median | 95% Confidence Interval | Cells/MicroL | 30 days and 90 days |
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| Secondary | 2 Year Post Transplant Overall Survival (OS) Rate | Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause . | All participants who received treatment | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
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Up to 5 years
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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 | Tacrolimus / Rapamycin | Tacrolimus / Rapamycin Tacrolimus / Rapamycin: Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily. | 3 | 37 | 0 | 37 | ||
| EG001 | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate Tacrolimus / Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance. | 2 | 37 | 0 | 37 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac General - Pericardial effusion | Cardiac disorders | CTCAE (3.0) | Systematic Assessment | Cardiac General - Pericardial effusion, Grade 3 |
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| Hemorrhage, GI-Lower GI NOS | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Hepatobiliary/Pancreas - Abdominal pain secondary to acute cholecystitis | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment | Hepatobiliary / Pancreas, Grade 3 Abdominal pain secondary to acute cholecystitis |
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| Renal / Genitourinary - Obstruction, GU Bladder | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | Obstruction, GU Bladder Grade 3 Bilateral ureteral obstruction secondary to clots |
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| Renal / Genitourinary - Renal Failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | Renal Failure Grade 3 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joseph Pidala | H. Lee Moffitt Cancer Center | 813-745-4673 | 2556 | Joseph.Pidala@moffitt.org |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D008727 | Methotrexate |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Participants |
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