Clinical Trial: HSCT for High Risk Inherited Inborn Errors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation

Brief Summary:

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

Detailed Summary: Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). However, 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), develop experience in kinetics of N-acetylcysteine, and evaluate biologic markers of oxidative status during transplantation. In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.
Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: Donor Cell Engraftment [ Time Frame: Day 42 ]

The process of transplanted stem cells reproducing new cells.


Original Primary Outcome: To evaluate the ability to achieve donor cell engraftment with related, unrelated and cord blood grafts using a Campath-1H, clofarabine, melphalan and low dose total body irradiation regimen.

Current Secondary Outcome:

  • Transplant Related Mortality [ 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.
  • Changes in Magnetic Resonance Imaging (MRI) [ Time Frame: Day 30, 60, 100 and 1 and 2 Years ]
  • Changes in Neuropsychometric Function [ Time Frame: 6 Months, 1 Year, 2 Years, 3 Years ]
  • Incidence of Acute Graft Versus Host Disease [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
  • Incidence of Chronic Graft Versus Host Disease [ Time Frame: 1 Year ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.


Original Secondary Outcome: determine the toxicity associated with this regimen, including neurologic, gastrointestinal, renal, pulmonary, cardiac and hepatic complications.

Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: September 29, 2006
Date Started: September 2006
Date Completion:
Last Updated: April 22, 2015
Last Verified: April 2015