Clinical trial NCT00176917: Stem Cell Transplantation for Hurler
Official title: Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mucopolysaccharidosis I
Mucopolysaccharidosis VI
Mannosidosis
Mucolipidosis Type II (I-cell Disease)
Keywords: stem cell transplant
storage disease
errors of metabolism
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 41
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for Hurler syndrome, Maroteaux Lamy syndrome, Mannosidosis, or I-cell disease.

Detailed description: Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman line four times daily for 4 days, Cyclophosphamide intravenously via the Hickman line once a day for 4 days, and Anti-Thymocyte Globulin IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to subjects to help the new marrow "take" and grow.

On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.

After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone or MMF are given to help prevent the complication of graft-versus-host disease and to decrease the chance that the new donor cells will be rejected.

Eligibility criteria: Inclusion Criteria:

* Patients with Mucopolysaccharidosis, type I (e.g., Hurler syndrome), Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or mismatched (at 1 antigen) related marrow, PBSC, or cord blood donor.
* Patients with Mucopolysaccharidosis, type I, Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or HLA-1 antigen mismatched unrelated marrow, PBSC, or HLA-0-2 antigen mismatched umbilical cord blood donor.
* Patients with MPS type I, Maroteaux Lamy Syndrome (MPS VI), or mucolipidosis type II (I-cell disease) will have a mental developmental index within two standard deviations of the normal mean, as best as can be determined using Bayley scales of infant development or other standardized testing, recognizing that these may be affected by speech and/or hearing impairment.
* Adequate organ function:
* Cardiac: ejection fraction \>40%; no decompensated congestive heart failure or uncontrolled arrhythmia
* Renal: serum creatinine \<2.0 mg/dl
* Hepatic: total bilirubin \<3x Upper limits of normal transaminases \< 5.0 x Upper limits of normal
* Signed consent.

Exclusion Criteria:

* Presence of major organ dysfunction (see above)
* Pregnancy
* Evidence of HIV infection or known HIV positive serology
* Patients or parents are psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance
* Patients \>50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD 34 cells/kg and therefore will not be eligible to receive unrelated PBSCs.

Primary outcomes:
measure: Mean Percentage of Donor Cells in Study Population (Chimerism).
timeFrame: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year
Secondary outcomes:
measure: Number of Patients Surviving on Study
timeFrame: at 100 days, 1 year, and 3 years post transplant
measure: Number of Patients Who Failed Engraftment.
timeFrame: Day 42 Post Transplant
measure: Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).
timeFrame: Day 100 Post Transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, MD
role: PRINCIPAL_INVESTIGATOR
References: