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| ID | Type | Description | Link |
|---|---|---|---|
| 0403M57728 | Other Identifier | IRB, University of Minnesota |
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The investigators hypothesize that weekly infusions of Laronidase ERT for 10-12 weeks prior to transplant and 8 weeks following transplant will result in a reduction of glycosaminoglycans (GAG) burden that is associated with decreased complications following transplant.
Subjects will receive laronidase once a week intravenously for 10-12 weeks prior to transplant and for approximately 8 weeks after transplant. Laronidase will be given by intravenous infusion (IV) through a catheter and from there to your child's body's cells and organs to break down the glycosaminoglycans (GAG) buildup.
Prior to starting ERT, subjects will have a complete physical examination, which includes a complete assessment of your child's airway and lungs. In addition to standard treatment evaluations and tests, which are done prior to hematopoietic stem cell transplant (HSCT), subjects will have the following tests: an additional teaspoon of blood for a baseline test for serum antibodies against laronidase, before and after the fourth dose of laronidase, the investigators will collect 2 teaspoons of blood for an alpha-L-iduronidase enzyme level; to watch for side effects to laronidase and the development of antibodies to laronidase, approximately 2 teaspoons of blood will be collected every 3 weeks while the subject is receiving laronidase ERT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Laronidase ERT Treatment | Experimental | Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stem Cell Transplant | Procedure | enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Alive at One Year Post Transplant | one year | |
| Number of Patients Requiring Ventilator Support at One Year Post Transplant | one year |
| Measure | Description | Time Frame |
|---|---|---|
| Donor Engraftment | Day 100 post transplant | |
| Patients With Grade III-IV Acute GVHD | Day 100 post transplant | |
| Reduction in Glycosaminoglycans (GAG) |
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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 | Laronidase ERT Treatment | Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant. Stem Cell Transplant: enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following Laronidase ERT: Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Laronidase ERT Treatment | Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant. Stem Cell Transplant: enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following Laronidase ERT: Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following. |
| 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 Patients Alive at One Year Post Transplant | Posted | Count of Participants | Participants | one year |
|
|
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An SAE as defined by the protocol includes unexpected: 1) laronidase related toxicity which is life threatening, requires hospitalization, causes persistent or significant disability/incapacity, causes congenital anomaly, is a medical event that may jeopardize the patent and require medical/surgical intervention to prevent one of the other outcomes, or causes death; 2) graft failure; 3) severe acute GVHD; and 4) severe regimen related toxicity grade III-IV, which includes mortality.
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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 | Laronidase ERT Treatment | Weekly infusion of laronidase enzyme replacement therapy followed by hematopoietic stem cell transplant. Stem Cell Transplant: enzyme replacement 10-12 weeks prior to hematopoietic stem cell transplant (HSCT), and 8 weeks following Laronidase ERT: Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Heart failure | Cardiac disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased Liver Function Test | Hepatobiliary disorders |
All of the patients on this trial also underwent allogeneic blood/marrow transplantation. All the serious and non-serious adverse events listed were related to the process of transplantation and not to the study medication, Laronidase.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paul Orchard | Masonic Cancer Center, University of Minnesota | (612) 626-2313 | orcha001@umn.edu |
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| ID | Term |
|---|---|
| D008059 | Mucopolysaccharidosis I |
| D008661 | Metabolism, Inborn Errors |
| ID | Term |
|---|---|
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D033581 | Stem Cell Transplantation |
| D007068 | Iduronidase |
| ID | Term |
|---|---|
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| Laronidase ERT | Drug | Laronidase ERT will be administered 10-12 weeks prior to HSCT, and 8 weeks following. |
|
|
Data was not collected on this outcome measure and is not available for reporting. |
| Prior to, During and After ERT |
| Toxicity (Adverse Events) Associated With Infusions of Laronidase | Data was not collected on this outcome measure and is not available for reporting. | 1 year post transplant |
| Development of Anti-iduronidase Antibodies in Serum | 1 Year |
| Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography | Baseline, 12 weeks after laronidase, after transplant |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Primary | Number of Patients Requiring Ventilator Support at One Year Post Transplant | Posted | Count of Participants | Participants | one year |
|
|
|
| Secondary | Donor Engraftment | Posted | Count of Participants | Participants | Day 100 post transplant |
|
|
|
| Secondary | Patients With Grade III-IV Acute GVHD | Posted | Count of Participants | Participants | Day 100 post transplant |
|
|
|
| Secondary | Reduction in Glycosaminoglycans (GAG) | Data was not collected on this outcome measure and is not available for reporting. | Data was not collected on this outcome measure and is not available for reporting. | Posted | Prior to, During and After ERT |
|
|
| Secondary | Toxicity (Adverse Events) Associated With Infusions of Laronidase | Data was not collected on this outcome measure and is not available for reporting. | Data was not collected on this outcome measure and is not available for reporting. | Posted | 1 year post transplant |
|
|
| Secondary | Development of Anti-iduronidase Antibodies in Serum | Data was not collected on this outcome measure and is not available for reporting. | Posted | 1 Year |
|
|
| Secondary | Patients With Improvement in Obstructive Apnea (Breathing) by Polysomnography | Data was not collected on this outcome measure and is not available for reporting. | Posted | Baseline, 12 weeks after laronidase, after transplant |
|
|
| 6 |
| 22 |
| 21 |
| 22 |
| Pericardial effusion | Cardiac disorders |
|
| Multiple system organ failure | General disorders |
|
| Other, Infection NOS | Infections and infestations |
|
| Catheter-related infection | Infections and infestations |
|
| Other, Upper respiratory Tract infection | Infections and infestations |
|
| Multifocal cerebral infarct | Nervous system disorders |
|
| Acute Respiratory Distress | Respiratory, thoracic and mediastinal disorders |
|
| Hyperbilirubinemia | Hepatobiliary disorders |
|
| Blood/Bone Marrow, NOS | Blood and lymphatic system disorders |
|
| Cerebrovascular Ischemia | Nervous system disorders |
|
| Cardiac, NOS | Cardiac disorders |
|
| Cholecystitis | Hepatobiliary disorders |
|
| Dehydration | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders |
|
| Fatigue | General disorders |
|
| Fracture, NOS | Musculoskeletal and connective tissue disorders |
|
| Hypoglycemia | Metabolism and nutrition disorders |
|
| Hemoglobin, NOS | Blood and lymphatic system disorders |
|
| Hemolysis | Blood and lymphatic system disorders |
|
| Hemorrhage, Pulmonary | Respiratory, thoracic and mediastinal disorders |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders |
|
| Infection with Grade 3 or 4 Neutrophils | Infections and infestations |
|
| Infection, NOS | Infections and infestations |
|
| Infection with Normal Neutrophils | Infections and infestations |
|
| Infection with Unknown Neutrophils | Infections and infestations |
|
| Mucositis, Pharynx | Respiratory, thoracic and mediastinal disorders |
|
| Necrosis, GI | Gastrointestinal disorders |
|
| Neurology, NOS | Nervous system disorders |
|
| Obstruction, Ureter | Renal and urinary disorders |
|
| Pain, Abdomen | Gastrointestinal disorders |
|
| Pain, Cardiac | Cardiac disorders |
|
| Pulmonary, NOS | Respiratory, thoracic and mediastinal disorders |
|
| Rash/Desquamation | Skin and subcutaneous tissue disorders |
|
| Renal, NOS | Renal and urinary disorders |
|
| Supraventricular and Nodal Arrythmia | Cardiac disorders |
|
| Syncope | Nervous system disorders |
|
| Thrombosis | Vascular disorders |
|
| Vascular, NOS | Vascular disorders |
|
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| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D014180 |
| Transplantation |
| D013514 | Surgical Procedures, Operative |
| D006026 | Glycoside Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |