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HSCT for High Risk Inherited Inborn Errors

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ClinicalTrials.gov Identifier: NCT00383448
Recruitment Status : Completed
First Posted : October 3, 2006
Results First Posted : July 11, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adrenoleukodystrophy
Metachromatic Leukodystrophy
Globoid Cell Leukodystrophy
Tay Sachs Disease
Sandhoffs Disease
Wolman Disease
I-Cell Disease
Sanfilippo Syndrome
GM1 Gangliosidosis
Interventions Drug: Clofarabine
Procedure: Total body Irradiation
Drug: Melphalan
Biological: Hematopoietic Stem Cell Transplantation
Drug: Alemtuzumab
Drug: mycophenylate mofetil
Device: Cyclosporine A
Drug: Hydroxyurea
Enrollment 38
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treated Patients
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 38
Completed 38
Not Completed 0
Arm/Group Title Treated Patients
Hide Arm/Group Description

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 Number of Baseline Participants 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
<=18 years
32
  84.2%
Between 18 and 65 years
6
  15.8%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Female
8
  21.1%
Male
30
  78.9%
1.Primary Outcome
Title Number of Patients With Donor Cell Engraftment
Hide Description Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
One patient was not evaluable due to an early death.
Arm/Group Title Treated Patients
Hide Arm/Group Description:

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 Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
26
  70.3%
2.Secondary Outcome
Title Number of Patients Whose Death Was Related to the Transplant
Hide Description In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treated Patients
Hide Arm/Group Description:

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 Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.3%
3.Secondary Outcome
Title Concentrations of Mycophenylate Mofetil (MMF)
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not collected on this outcome measure and is not available for reporting.
Arm/Group Title Treated Patients
Hide Arm/Group Description:
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Patients With Acute Graft Versus Host Disease (GVHD)
Hide Description Graft-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.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treated Patients
Hide Arm/Group Description:

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 Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
3
   7.9%
5.Secondary Outcome
Title Number of Patients With Chronic Graft Versus Host Disease (GVHD)
Hide Description Graft-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.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treated Patients
Hide Arm/Group Description:

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 Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.3%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treated Patients
Hide Arm/Group Description

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.

All-Cause Mortality
Treated Patients
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Treated Patients
Affected / at Risk (%)
Total   10/38 (26.32%) 
General disorders   
Death Due to Disease Progression  2/38 (5.26%) 
Disease Progression  4/38 (10.53%) 
Graft Failure  4/38 (10.53%) 
Infections and infestations   
Infection with Grade 3 or 4 Neutrophils  1/38 (2.63%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treated Patients
Affected / at Risk (%)
Total   33/38 (86.84%) 
Blood and lymphatic system disorders   
Hemolytic Anemia  2/38 (5.26%) 
Cardiac disorders   
Pericardial Effusion  7/38 (18.42%) 
Ear and labyrinth disorders   
Requires Myringotomy, NOS  3/38 (7.89%) 
Gastrointestinal disorders   
Bloody Stool  2/38 (5.26%) 
Pneumatosis Coli  2/38 (5.26%) 
General disorders   
Aseptic/Avascular Necrosis, NOS  2/38 (5.26%) 
Requires Hemodialysis, NOS  2/38 (5.26%) 
Hepatobiliary disorders   
Veno-Oclusive Disease  2/38 (5.26%) 
Infections and infestations   
Bacterial Infection, Feces  10/38 (26.32%) 
Bacterial Infection, Blood  12/38 (31.58%) 
Pneumonia  14/38 (36.84%) 
Fungal Infection, Skin  2/38 (5.26%) 
Otitis Media  2/38 (5.26%) 
Fungal Infection, Respiratory  3/38 (7.89%) 
Viral Infection, Skin  3/38 (7.89%) 
Sinusitis  3/38 (7.89%) 
Upper Respiratory Infection  3/38 (7.89%) 
Bacterial Infection, Skin  4/38 (10.53%) 
Fungal Infection, Blood  4/38 (10.53%) 
Viral Infection, Feces  4/38 (10.53%) 
Bacterial Infection, Urine  5/38 (13.16%) 
Viral Infection, Respiratory  6/38 (15.79%) 
Viral Infection, Blood  7/38 (18.42%) 
Metabolism and nutrition disorders   
Hyperglycemia  3/38 (7.89%) 
Nervous system disorders   
Cerebral and Cerebellar Atrophy  2/38 (5.26%) 
Neuropathy  2/38 (5.26%) 
Seizures  8/38 (21.05%) 
Renal and urinary disorders   
Cystitis, NOS  5/38 (13.16%) 
Reproductive system and breast disorders   
Pulmonary Consolidation  2/38 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory Failure  2/38 (5.26%) 
Pulmonary Opacities  3/38 (7.89%) 
Requires Intubation, NOS  9/38 (23.68%) 
Vascular disorders   
Capillary Leak  2/38 (5.26%) 
Hypertension  6/38 (15.79%) 

Because the diseases being treated on this study are rare, our intent was to only report these outcomes in context with other protocols.

The data was collected, but is not interpretable without combining the data with additional studies.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Paul Orchard
Organization: Masonic Cancer Center, University of Minnesota
Phone: 612-626-2313
EMail: orcha001@umn.edu
Layout table for additonal information
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00383448    
Other Study ID Numbers: MT2006-14
0606M87246 ( Other Identifier: IRB, University of Minnesota )
First Submitted: September 29, 2006
First Posted: October 3, 2006
Results First Submitted: March 31, 2017
Results First Posted: July 11, 2019
Last Update Posted: July 11, 2019