Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01626092|
Recruitment Status : Completed
First Posted : June 22, 2012
Results First Posted : October 11, 2016
Last Update Posted : December 5, 2017
|Condition or disease||Intervention/treatment||Phase|
|Lysosomal Storage Disease Peroxisomal Disorder||Drug: Campath-1H Drug: Clofarabine Drug: Melphalan Radiation: Total Body Irradiation with Marrow Boosting Biological: Hematopoietic stem cell transplantation Drug: Cyclosporine A Drug: Mycophenolate mofetil||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 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 Cell Transplantation and Low-Dose Total Body Irradiation With Marrow Boosting by Volumetric-Modulated Arc Therapy (VMAT)|
|Actual Study Start Date :||July 11, 2012|
|Actual Primary Completion Date :||November 2013|
|Actual Study Completion Date :||November 2013|
Experimental: Intent-To-Treat Patients
Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.
A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.
Other Name: alemtuzumab-1HDrug: Clofarabine
A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,
-8, -7, -6, and -5.
Other Name: ClolarDrug: Melphalan
A single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes.
Other Name: AlkeranRadiation: Total Body Irradiation with Marrow Boosting
Other Name: Volumetric-Modulated Arc Therapy (VMAT)Biological: Hematopoietic stem cell transplantation
Patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability.Drug: Cyclosporine A
Patients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose 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 200 mg/L to 400 mg/L.
Other Name: CsADrug: Mycophenolate mofetil
Patients will receive mycophenolate mofetil (MMF) therapy beginning on day -3. Dosing of MMF will be 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg/dose three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Other Name: MMF
- Donor (Allogeneic) Hematopoietic Engraftment [ Time Frame: Day 100 Following Hematopoietic Cell Transplant (HCT) ]Number of patients who achieve hematopoietic engraftment - assessment of nucleated peripheral blood cells for donor (allogeneic) chimerism following this reduced-intensity HCT.
- Transplant-Related Mortality [ Time Frame: Day 100 following HCT ]Incidence of death due to complications of HCT following this reduced-intensity conditioning regimen.
- Neurologic Outcomes [ Time Frame: Changes from Baseline, Days 30, 60, 100, Year 1, Year 2, Year 3 Following HCT ]Depending upon underlying primary disease, a combination of evaluative tools (e.g. brain magnetic resonance imaging (MRI), clinical neurologic exam, neuropsychologic testing, electromyography) will be applied for assessment of neurologic function and how it may be affected by this reduced-intensity HCT regimen.
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): NCT01626092
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Weston Miller, MD||Masonic Cancer Center, University of Minnesota|