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| ID | Type | Description | Link |
|---|---|---|---|
| MT2009-19 | Other Identifier | Blood and Marrow Transplantation Program |
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Rationale: Chemotherapy administration before a donor stem cell transplant is necessary to stop the patient's immune system from rejecting the donor's stem cells. When healthy stem cells from a donor are infused into the patient, the donor white blood cells can provide the missing enzyme that causes the metabolic disease. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. This may be an effective treatment for inherited metabolic disorders.
Purpose: The design of this study is to achieve donor cell engraftment in patients with standard-risk inherited metabolic diseases with limited peri-transplant morbidity and mortality. This will be achieved through the administration of the chemotherapy regimen described. The intention is to follow transplanted patient for years after transplant monitoring them for complications of their disease and assisting families with a multifaceted interdisciplinary approach.
Primary Objective:
Secondary Objectives:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transplant Patients | Experimental | Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Campath-1H | Drug | Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV) |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Donor Derived Engraftment | Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells. | Day 100 Post Transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Orchard, MD | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Transplant Patients | Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Cyclophosphamide | Drug | Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily. |
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| Busulfan | Drug | Administered every 6 hours: If < or = 12 kg then 1.1 mg/kg/dose intravenous (IV). If > 12 kg then 0.8 mg/kg/dose IV |
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| Allogeneic stem cell transplantation | Procedure | Administered > 24 hours after last dose of busulfan. |
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| Cyclosporine A | Drug | 2.5 mg/kg/dose intravenous (IV_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight:
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| Mycophenolate Mofetil | Drug | 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: The same dosage is used orally or intravenously. Stop MMF at day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later. |
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| Day 100 Post Transplant |
| Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Day 100 Post Transplant |
| Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Day 100 Post Transplant |
| Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Day 100 Post Transplant |
| Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Day 100 Post Transplant |
| Number of Patients Who Died Peri-Transplant | Peri-transplant is defined as within 100 days of transplant. | By Day 100 Post Transplant |
| Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Day 28 |
| Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Day 42 |
| Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Day 100 |
| Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | 6 months |
| Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | One year |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Transplant Patients | Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later. |
| 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, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | 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 Patients With Donor Derived Engraftment | Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells. | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD) | GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4 | Posted | Count of Participants | Participants | Day 100 Post Transplant |
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| Secondary | Number of Patients Who Died Peri-Transplant | Peri-transplant is defined as within 100 days of transplant. | Posted | Count of Participants | Participants | By Day 100 Post Transplant |
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| Secondary | Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 28 |
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| Secondary | Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 42 |
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| Secondary | Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 100 |
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| Secondary | Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Posted | Mean | Standard Deviation | percentage of donor cells | 6 months |
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| Secondary | Donor Cell Chimerism Following Transplant | Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin. | Posted | Mean | Standard Deviation | percentage of donor cells | One 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 | Transplant Patients | Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later. | 8 | 46 | 40 | 46 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericardial Effusion | Cardiac disorders |
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| Renal Failure | Renal and urinary disorders |
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| Diarrhea | Gastrointestinal disorders |
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| Respiratory Failure | Respiratory, thoracic and mediastinal disorders |
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| Pulmonary Veno-Occlusive Disease | Respiratory, thoracic and mediastinal disorders |
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| Cardiac Arrest | Cardiac disorders |
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| Intracerebral Hemorrhage | Nervous system disorders |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Metabolism and nutrition disorders |
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| Bilirubin Increased | Investigations |
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| Diarrhea | Gastrointestinal disorders |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders |
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| Fever | General disorders |
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| Graft Versus Host Disease | General disorders |
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| Headache | Nervous system disorders |
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| Hemorrhage, Gastrointestinal | Gastrointestinal disorders |
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| Hemorrhage, Genitourinary | Renal and urinary disorders |
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| Hives | Skin and subcutaneous tissue disorders |
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| Hypertension | Vascular disorders |
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| Hypotension | Vascular disorders |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders |
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| Infection, NOS | Infections and infestations |
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| Infection, Respiratory | Infections and infestations |
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| Mucositis | Gastrointestinal disorders |
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| Nausea | Gastrointestinal disorders |
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| Pericardial Effusion | Cardiac disorders |
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| Rash | Skin and subcutaneous tissue disorders |
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| Tachycardia | Cardiac disorders |
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| Vomiting | Gastrointestinal disorders |
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| Infection, Gastrointestinal | Infections and infestations |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paul Orchard | Masonic Cancer Center, University of Minnesota | 612-626-2313 | orcha001@umn.edu |
| ID | Term |
|---|---|
| D009083 | Mucopolysaccharidoses |
| D008059 | Mucopolysaccharidosis I |
| D016532 | Mucopolysaccharidosis II |
| D009087 | Mucopolysaccharidosis VI |
| D016538 | Mucopolysaccharidosis VII |
| D008363 | alpha-Mannosidosis |
| D005645 | Fucosidosis |
| D054880 | Aspartylglucosaminuria |
| D000326 | Adrenoleukodystrophy |
| D007965 | Leukodystrophy, Globoid Cell |
| D007966 | Leukodystrophy, Metachromatic |
| D013106 | Sphingolipidoses |
| D018901 | Peroxisomal Disorders |
| ID | Term |
|---|---|
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D044904 | Mannosidase Deficiency Diseases |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D056784 | Leukoencephalopathies |
| D003711 | Demyelinating Diseases |
| D000309 | Adrenal Insufficiency |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D052439 | Lipid Metabolism Disorders |
| D052516 | Sulfatidosis |
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| ID | Term |
|---|---|
| D000074323 | Alemtuzumab |
| D003520 | Cyclophosphamide |
| D002066 | Busulfan |
| D033581 | Stem Cell Transplantation |
| D016572 | Cyclosporine |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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