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| ID | Type | Description | Link |
|---|---|---|---|
| 0808M42261 | Other Identifier | Masonic Cancer Center, University of Minnesota |
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The purpose of this research is to explore what we believe may be a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors.
This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| marrow graft transplant conditioning | Active Comparator | Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. |
|
| cord blood transplant conditioning | Active Comparator | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| umbilical cord blood transplantation | Procedure | Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Achieved Donor Cell Engraftment | Day 100 |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant Related Mortality at 100 Days | day 100 | |
| Transplant Related Toxicity | Day 100 post transplant | |
| Incidence of Grade II - IV Acute Graft-versus-host Disease |
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Inclusion Criteria:
Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
the need for ongoing transfusions, OR
the presence of progressive anemia or thrombocytopenia, OR
a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.
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 |
|---|---|---|---|---|---|---|
| University of MInnesota, Fairview | Minneapolis | Minnesota | 55455 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Marrow Graft Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only. |
| FG001 | Cord Blood Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Marrow Graft Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only. |
| 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 Who Achieved Donor Cell Engraftment | Posted | Count of Participants | Participants | Day 100 |
|
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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 | Marrow Graft Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Multi-Organ Failure | General disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders |
Because the disease being treated on this study is rare, our intent was to only report these outcomes in context with other protocols. At some point in the future if we have enough patients we will analyze the data.
| 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 |
|---|---|
| D010022 | Osteopetrosis |
| ID | Term |
|---|---|
| D010026 | Osteosclerosis |
| D010009 | Osteochondrodysplasias |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
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| ID | Term |
|---|---|
| D036101 | Cord Blood Stem Cell Transplantation |
| D000074323 | Alemtuzumab |
| D003520 | Cyclophosphamide |
| D002066 | Busulfan |
| C042382 | fludarabine phosphate |
| ID | Term |
|---|---|
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
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|
|
| Campath-1H | Drug | Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. |
|
|
| Total Lymphoid Irradiation | Radiation | Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). |
|
|
| Cyclophosphamide | Drug | Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only. |
|
|
| Busulfan | Drug | patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. |
|
|
| Fludarabine monophosphate | Drug | Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only. |
|
|
| marrow graft transplantation | Procedure | Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42. |
|
|
| by Day 100 after transplant |
| BG001 | Cord Blood Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Cord Blood Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving |
|
|
| Secondary | Transplant Related Mortality at 100 Days | Posted | Count of Participants | Participants | day 100 |
|
|
|
| Secondary | Transplant Related Toxicity | Posted | Count of Participants | Participants | Day 100 post transplant |
|
|
|
| Secondary | Incidence of Grade II - IV Acute Graft-versus-host Disease | Posted | Count of Participants | Participants | by Day 100 after transplant |
|
|
|
| 3 |
| 6 |
| 6 |
| 6 |
| EG001 | Cord Blood Transplant Conditioning | Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving | 0 | 1 | 1 | 1 |
| Myocarditis | Cardiac disorders |
|
| Acute Graft versus Host Disease | General disorders |
|
| Acute Sinusitis | Infections and infestations |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders |
|
| Autoimmune Hemolytic Anemia | Blood and lymphatic system disorders |
|
| Bacterial Infection, Blood | Infections and infestations |
|
| Bacterial Infection, Respiratory | Infections and infestations |
|
| Bacterial Infection, Feces | Infections and infestations |
|
| Capillary Leak | Vascular disorders |
|
| Blood Clot in Bladder Wall | Blood and lymphatic system disorders |
|
| Requires Continuous Veno-Venous Hemofiltration, NOS | Renal and urinary disorders |
|
| Cystitis | Infections and infestations |
|
| Complete Heart Block | Cardiac disorders |
|
| Fungal Infection, Blood | Infections and infestations |
|
| Fungal Infection, Respiratory | Infections and infestations |
|
| Fungal Infection, Feces | Infections and infestations |
|
| Fungal Infection, Urine | Infections and infestations |
|
| Further Decompression of Lateral and Third Ventricles | Nervous system disorders |
|
| Requires Hemodialysis, NOS | Renal and urinary disorders |
|
| Hypertension | Vascular disorders |
|
| Hyperechogenic Renomegaly with Ascites | Renal and urinary disorders |
|
| Hyperglycemia | Metabolism and nutrition disorders |
|
| Intracranial Hemorrhage | Nervous system disorders |
|
| Intraparenchymal Bleed | Nervous system disorders |
|
| Requires Intubation, NOS | Respiratory, thoracic and mediastinal disorders |
|
| Large Splenic Infarct | Blood and lymphatic system disorders |
|
| Sinus Infection | Infections and infestations |
|
| Low Lung Volumes | Respiratory, thoracic and mediastinal disorders |
|
| Obstruction of Left Proximal Internal Jugular Vein | Vascular disorders |
|
| Papilledema and Retinal Hemorrhages Leading to Blindness | Eye disorders |
|
| Partial Small Bowel Obstruction | Gastrointestinal disorders |
|
| Pericardial Effusion | Cardiac disorders |
|
| Placement of Epicardial Ventricular Pacing Wire | Cardiac disorders |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders |
|
| Posterior Reversible Encephalopathy Syndrome | Nervous system disorders |
|
| Pulmonary Hemorrhage | Respiratory, thoracic and mediastinal disorders |
|
| Pulmonary Hypertension | Respiratory, thoracic and mediastinal disorders |
|
| Reactive Airway Disease | Respiratory, thoracic and mediastinal disorders |
|
| Renal Failure | Renal and urinary disorders |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders |
|
| Seizure | Nervous system disorders |
|
| Small Bowel Ascites | Gastrointestinal disorders |
|
| Subconjunctival Hemorrhages | Eye disorders |
|
| Upper Respiratory Infection | Infections and infestations |
|
| Viral Infection, Blood | Infections and infestations |
|
| Viral Infection, Myocardium | Infections and infestations |
|
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| D009140 |
| Musculoskeletal Diseases |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| 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 |