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| ID | Type | Description | Link |
|---|---|---|---|
| R01CA132197-06A2 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".
The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.
The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| First Study Stage: Study Treatment | Experimental | Visilizumab, Tacrolimus and Methotrexate. |
|
| Second Study Stage: Standard Treatment | Active Comparator | Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Visilizumab | Drug | 3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant). |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days | Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned. Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II | 100 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Epstein-Barr Virus (EBV) Reactivation | Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels > 1000 copies per ml plasma were scored as positive. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lia Perez, MD | H. Lee Moffitt Cancer Center and Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center & Research Institute | Tampa | Florida | 33612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21874061 | Derived | Pidala J, Perez L, Beato F, Anasetti C. Ustekinumab demonstrates activity in glucocorticoid-refractory acute GVHD. Bone Marrow Transplant. 2012 May;47(5):747-8. doi: 10.1038/bmt.2011.172. Epub 2011 Aug 29. No abstract available. |
| Label | URL |
|---|---|
| H. Lee Moffitt Cancer Center \& Research Institute | View source |
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The study was closed during the single-arm, first stage and did not proceed to the second stage comparison to antithymocyte globulin (ATG) in combination with tacrolimus/methotrexate as originally planned.
Participants were enrolled at Moffitt Cancer Center between February 2008 and April 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | First Study Stage: Study Treatment | Visilizumab, Tacrolimus and Methotrexate. All participants. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Tacrolimus | Drug | 0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant. |
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| Methotrexate | Drug | 15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant. |
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| Antithymocyte globulin (ATG) | Drug | 1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant. |
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| Tacrolimus | Drug | 0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant. |
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| Methotrexate | Drug | 15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant. |
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| Incidence of Rituximab Response to Reactivated EBV Without PTLD |
Participants who developed plasma EBV-DNA of >1000 copies/mL on any tests received rituximab. Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD). |
| 100 days |
| Overall Survival (OS) | Median OS in days. Survival was measured from the time of transplant to the time of death. | At 2 years and 5 years |
| Pharmacodynamics of Visilizumab - Test 1 | Mean Cmax (±SD) | At 1 - 2 hours |
| Pharmacodynamics of Visilizumab - Test 2 | Mean terminal half-life (±SD) | Up to 205 hours |
| COMPLETED |
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| NOT COMPLETED |
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First Stage: Study Treatment. All participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | First Stage: Study Treatment | Visilizumab, Tacrolimus and Methotrexate. All participants. |
| 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 | Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days | Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned. Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II | All participants | Posted | Number | participants | 100 days |
|
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| Secondary | Incidence of Epstein-Barr Virus (EBV) Reactivation | Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels > 1000 copies per ml plasma were scored as positive. | All participants | Posted | Number | participants | 3 months |
|
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| Secondary | Incidence of Rituximab Response to Reactivated EBV Without PTLD | Participants who developed plasma EBV-DNA of >1000 copies/mL on any tests received rituximab. Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD). | Reactivated EBV participants | Posted | Number | participants | 100 days |
|
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| Secondary | Overall Survival (OS) | Median OS in days. Survival was measured from the time of transplant to the time of death. | Participants who had died by Year 2 and additional participants who had died by Year 5. | Posted | Median | Full Range | days | At 2 years and 5 years |
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| Secondary | Pharmacodynamics of Visilizumab - Test 1 | Mean Cmax (±SD) | All participants | Posted | Mean | Standard Deviation | ng/mL | At 1 - 2 hours |
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| Secondary | Pharmacodynamics of Visilizumab - Test 2 | Mean terminal half-life (±SD) | All participants | Posted | Mean | Standard Deviation | hours | Up to 205 hours |
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5 years
The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
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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 | First Stage: Study Treatment | Visilizumab, Tacrolimus and Methotrexate. All participants. | 8 | 8 | 0 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hemorrhage, GI - Colon | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Febrile neutropenia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Infection - Blood | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Infection - Bronchus | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Adult Respiratory Distress Syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Pulmonary/Upper Respiratory - Other - pseudomonas pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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Study closed early during the first stage, did not proceed to the second stage comparison as planned. Investigators exercised right to close the study prematurely for lack of efficacy, although no protocol-defined end points had been met.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lia Perez, M.D. | H. Lee Moffitt Cancer Center and Research Institute | 813-745-7202 | lia.perez@moffitt.org |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D019337 | Hematologic Neoplasms |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D009190 | Myelodysplastic Syndromes |
| D055728 | Primary Myelofibrosis |
| D000741 | Anemia, Aplastic |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D009196 | Myeloproliferative Disorders |
| D000740 | Anemia |
| D000080983 | Bone Marrow Failure Disorders |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| C456519 | visilizumab |
| D016559 | Tacrolimus |
| D008727 | Methotrexate |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| 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 |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| >=65 years |
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