Trial Outcomes & Findings for HSCT for High Risk Inherited Inborn Errors (NCT NCT00383448)
NCT ID: NCT00383448
Last Updated: 2019-07-11
Results Overview
Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
38 participants
Primary outcome timeframe
Day 100
Results posted on
2019-07-11
Participant Flow
Participant milestones
| Measure |
Treated Patients
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
HSCT for High Risk Inherited Inborn Errors
Baseline characteristics by cohort
| Measure |
Treated Patients
n=38 Participants
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
|
Age, Categorical
<=18 years
|
32 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 100Population: One patient was not evaluable due to an early death.
Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.
Outcome measures
| Measure |
Treated Patients
n=37 Participants
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
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Number of Patients With Donor Cell Engraftment
|
26 Participants
|
SECONDARY outcome
Timeframe: Day 100In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Outcome measures
| Measure |
Treated Patients
n=38 Participants
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
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Number of Patients Whose Death Was Related to the Transplant
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 3Population: Data was not collected on this outcome measure and is not available for reporting.
MMF levels are to be sent on day +3 to the main laboratory for determinations of MMF kinetics. Data was not collected on this outcome measure and is not available for reporting.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 100Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Acute GVHD can occur once the donor's cells have engrafted in the transplant recipient. The symptoms typically appear within weeks after transplant.
Outcome measures
| Measure |
Treated Patients
n=38 Participants
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
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Number of Patients With Acute Graft Versus Host Disease (GVHD)
|
3 Participants
|
SECONDARY outcome
Timeframe: 1 yearGraft-Versus-Host Disease is a severe complication created by infusion of donor cells into a foreign host. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.
Outcome measures
| Measure |
Treated Patients
n=38 Participants
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
|
Number of Patients With Chronic Graft Versus Host Disease (GVHD)
|
2 Participants
|
Adverse Events
Treated Patients
Serious events: 10 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treated Patients
n=38 participants at risk
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
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General disorders
Death Due to Disease Progression
|
5.3%
2/38
|
|
General disorders
Disease Progression
|
10.5%
4/38
|
|
Infections and infestations
Infection with Grade 3 or 4 Neutrophils
|
2.6%
1/38
|
|
General disorders
Graft Failure
|
10.5%
4/38
|
Other adverse events
| Measure |
Treated Patients
n=38 participants at risk
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Clofarabine: days -7 through -3: 40 mg/m\^2 intravenously over 2 hours
Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Melphalan: day -2: 140 mg/m\^2 intravenously over 30 minutes
Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0
Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8
mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
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|---|---|
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Infections and infestations
Bacterial Infection, Feces
|
26.3%
10/38
|
|
Infections and infestations
Bacterial Infection, Blood
|
31.6%
12/38
|
|
Infections and infestations
Pneumonia
|
36.8%
14/38
|
|
Infections and infestations
Fungal Infection, Skin
|
5.3%
2/38
|
|
General disorders
Aseptic/Avascular Necrosis, NOS
|
5.3%
2/38
|
|
Gastrointestinal disorders
Bloody Stool
|
5.3%
2/38
|
|
Vascular disorders
Capillary Leak
|
5.3%
2/38
|
|
Nervous system disorders
Cerebral and Cerebellar Atrophy
|
5.3%
2/38
|
|
General disorders
Requires Hemodialysis, NOS
|
5.3%
2/38
|
|
Blood and lymphatic system disorders
Hemolytic Anemia
|
5.3%
2/38
|
|
Nervous system disorders
Neuropathy
|
5.3%
2/38
|
|
Infections and infestations
Otitis Media
|
5.3%
2/38
|
|
Gastrointestinal disorders
Pneumatosis Coli
|
5.3%
2/38
|
|
Reproductive system and breast disorders
Pulmonary Consolidation
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
5.3%
2/38
|
|
Hepatobiliary disorders
Veno-Oclusive Disease
|
5.3%
2/38
|
|
Infections and infestations
Fungal Infection, Respiratory
|
7.9%
3/38
|
|
Infections and infestations
Viral Infection, Skin
|
7.9%
3/38
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.9%
3/38
|
|
Ear and labyrinth disorders
Requires Myringotomy, NOS
|
7.9%
3/38
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Opacities
|
7.9%
3/38
|
|
Infections and infestations
Sinusitis
|
7.9%
3/38
|
|
Infections and infestations
Upper Respiratory Infection
|
7.9%
3/38
|
|
Infections and infestations
Bacterial Infection, Skin
|
10.5%
4/38
|
|
Infections and infestations
Fungal Infection, Blood
|
10.5%
4/38
|
|
Infections and infestations
Viral Infection, Feces
|
10.5%
4/38
|
|
Infections and infestations
Bacterial Infection, Urine
|
13.2%
5/38
|
|
Renal and urinary disorders
Cystitis, NOS
|
13.2%
5/38
|
|
Infections and infestations
Viral Infection, Respiratory
|
15.8%
6/38
|
|
Vascular disorders
Hypertension
|
15.8%
6/38
|
|
Infections and infestations
Viral Infection, Blood
|
18.4%
7/38
|
|
Cardiac disorders
Pericardial Effusion
|
18.4%
7/38
|
|
Nervous system disorders
Seizures
|
21.1%
8/38
|
|
Respiratory, thoracic and mediastinal disorders
Requires Intubation, NOS
|
23.7%
9/38
|
Additional Information
Dr. Paul Orchard
Masonic Cancer Center, University of Minnesota
Phone: 612-626-2313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place