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
Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). This protocol also considers other inherited metabolic diseases such as, but not limited to, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome or Sandhoff disease, I-cell disease (mucolipidosis II).
For patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, 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 pharmacokinetics of clofarabine and mycophenolate mofetil (MMF). In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.
|Condition or disease||Intervention/treatment||Phase|
|Adrenoleukodystrophy Metachromatic Leukodystrophy Globoid Cell Leukodystrophy Tay Sachs Disease Sandhoffs Disease Wolman Disease I-Cell Disease Sanfilippo Syndrome GM1 Gangliosidosis||Drug: Clofarabine Procedure: Total body Irradiation Drug: Melphalan Biological: Hematopoietic Stem Cell Transplantation Drug: Alemtuzumab Drug: mycophenylate mofetil Device: Cyclosporine A Drug: Hydroxyurea||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation|
|Study Start Date :||September 2006|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||September 2014|
Experimental: Treated Patients
Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
days -7 through -3: 40 mg/m^2 intravenously over 2 hours
Other Name: Clolar
Procedure: 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.
Other Name: TLI
day -2: 140 mg/m^2 intravenously over 30 minutes
Other Name: Alkeran
Biological: Hematopoietic Stem Cell Transplantation
receives infusion of stem cells on day 0
0.3 mg/kg intravenously (IV) days -12 through -8
Other Name: Campath 1-H
Drug: 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. Consider dose modification if renal impairment (GFR<25 mL/minute corrected)
Other Name: MMF
Device: Cyclosporine A
Patients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose intravenously (IV); if the recipient body weight is <40 kg, dosing will be 3 times daily, and if > 40 kg twice daily. An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2.5 x the current IV dose (maximum 12.5 mg/kg/day as initial oral dose).
CsA taper begins at day +100.
Other Name: CsA
hydroxyurea (HU) beginning day -28 and continuing through alemtuzumab administration
- Number of Patients With Donor Cell Engraftment [ Time Frame: Day 100 ]Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.
- Number of Patients Whose Death Was Related to the Transplant [ Time Frame: Day 100 ]In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
- Concentrations of Mycophenylate Mofetil (MMF) [ Time Frame: Day 3 ]
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.
- Number of Patients With Acute Graft Versus Host Disease (GVHD) [ Time Frame: Day 100 ]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.
- Number of Patients With Chronic Graft Versus Host Disease (GVHD) [ Time Frame: 1 year ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00383448
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Paul Orchard, MD||Masonic Cancer Center, University of Minnesota|