Stem Cell Transplant for Inborn Errors of Metabolism

Adrenoleukodystrophy Clinical Trial

Official title:

Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176904
• Other study ID #: MT1995-01
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 12, 2005
• Last updated: December 3, 2017
• Start date: January 1995
• Est. completion date: June 2010

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 an inherited metabolic storage disease.

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 (ATG) intravenously (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.

Other known NCT identifiers

• NCT00005894

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, Gaucher's disease, Fucosidosis, Wolman disease, Niemann-Pick disease and Batten disease (CLN3) who have a human leukocyte antigen (HLA)-identical or haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor. One or two umbilical cord blood (UCB) units may be used.

• Patients with GM1 gangliosidosis, Tay Sachs disease or Sandhoff disease who have a HLA-identical or 1 antigen mismatched related or unrelated donor, or suitably matched umbilical cord blood unit(s). One or two UCB units may be used.

• Patients with adrenoleukodystrophy must have magnetic resonance imaging (MRI) findings, neurological and neuropsychometric function consistent with the diagnosis, and for boys with parietal-occipital dysmyelination a performance intelligence quotient (IQ) =80. In cases, when the performance IQ is not =80, the protocol committee may recommend transplant if the patient's clinical condition and neuropsychometric status are deemed to be acceptable based upon consideration of such factors as age at onset of cerebral disease, magnitude of change in performance IQ and neurologic deficits.

• Patients with arylsulfatase A deficiency (Metachromatic Leukodystrophy) must have either the presymptomatic late infantile, juvenile or adult form of the disease and must have acceptable neurological and neuropsychometric function.

• Patients with galactocerebrosidase deficiency (Globoid Cell Leukodystrophy) must have acceptable neurological and neuropsychometric function.

• Patients with acid lipase deficiency (Wolman disease) must have a liver biopsy that documents no evidence of hepatic cirrhosis, and acceptable neurological and neuropsychometric function.

• Patients with fucosidase deficiency (Fucosidosis) must have acceptable neurological and neuropsychometric function.

• Patients with glucocerebrosidase deficiency (Gaucher's Disease) must have acceptable neurologic and neuropsychometric function.

• Patients with Batten's disease (CLN3) must have acceptable Neurological and neuropsychometric function.

• Absence of major organ dysfunction. Organ evaluation results as follows:

• Cardiac: ejection fraction >30%

• Renal: serum creatinine <2x normal or creatinine clearance 60 mL/min.

• Hepatic: total bilirubin <2x normal and Aspartate aminotransferase (AST) <2x normal

• Signed consent.

Exclusion Criteria:

• Patients with symptomatic late infantile form of metachromatic leukodystrophy.

• Patients with symptomatic infantile globoid leukodystrophy.

• Note: Patients with Hurler syndrome, mucopolysaccharidosis (MPS) VI, or Mannosidosis disease are no longer eligible for this protocol, but can be transplanted under protocol MT 9907 (NCT00176917 - Hematopoietic Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)).

• Pregnancy

• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology

• Patients or parents are psychologically incapable of undergoing bone marrow transplant (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 10^6 CD34 cells/kg and therefore will not be eligible to receive unrelated peripheral blood stem cells (PBSCs)

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• Aphasia, Primary Progressive
• Batten Disease
• Frontotemporal Dementia
• Fucosidosis
• Gangliosidoses
• Gangliosidosis, GM1
• Gaucher Disease
• Gaucher's Disease
• Globoid Cell Leukodystrophy
• GM1 Gangliosidosis
• Leukodystrophy, Globoid Cell
• Leukodystrophy, Metachromatic
• Metabolism, Inborn Errors
• Metachromatic Leukodystrophy
• Neuronal Ceroid-Lipofuscinoses
• Niemann-Pick Disease
• Niemann-Pick Disease, Type C
• Niemann-Pick Diseases
• Pick Disease of the Brain
• Sandhoff Disease
• Tay Sachs Disease
• Tay-Sachs Disease
• Wolman Disease

Intervention

Procedure:
• Stem Cell Transplant
The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains an enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic cells can come from bone marrow, peripheral blood (i.e., the blood circulating in our body's blood vessels) or umbilical cord blood (i.e., blood taken from the umbilical cord after a baby is born and umbilical cord is cut).

Drug:
• Busulfan, Cyclophosphamide, Antithymocyte Globulin
Subjects will receive BUSULFAN intravenously (IV)- patients < or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients > 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) via the Hickman line twice daily for three days before the transplant. These three drugs are being given to help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Number of patients alive at designated timepoints after transplant.	100 Days, 1 Year and 3 Years
Secondary	Overall Donor Engraftment	Number of patients with full donor chimerism (state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease) by Day 100 post-transplant of at least 90%.	Day 100
Secondary	Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease	Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.	Day 100
Secondary	Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease	Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.	Day 100
Secondary	Number of Patients With Chronic Graft-Versus-Host Disease	Number of patients who exhibited chronic graft-versus-host disease by 1 Year post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Chronic GVHD is an extension of this syndrome.	1 Year Post Transplant