Stem Cell Transplantation for Hurler - Full Text View

Sponsored by:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176917

Purpose

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.

Condition	Intervention	Phase
Mucopolysaccharidosis I Mucopolysaccharidosis VI Mannosidosis Mucolipidosis Type II (I-cell Disease)	Procedure: Stem Cell Transplant Drug: Busulfan, Cyclophosphamide, ATG	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-mannosidosis mucolipidosis II alpha/beta mucopolysaccharidosis type I succinic semialdehyde dehydrogenase deficiency

Drug Information available for: Cyclophosphamide Busulfan

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Mean Percentage of Donor Cells in Study Population (Chimerism). [ Time Frame: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Patients Surviving on Study [ Time Frame: at 100 days, 1 year, and 3 years post transplant ] [ Designated as safety issue: Yes ]
Number of Patients Who Failed Engraftment. [ Time Frame: Day 42 Post Transplant ] [ Designated as safety issue: Yes ]
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD). [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: Yes ]

Enrollment:	41
Study Start Date:	May 1999
Estimated Study Completion Date:	May 2010
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment Arm: Experimental All patients treated with chemotherapy and transplantation.	Procedure: Stem Cell Transplant The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains the 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, ATG Prior to transplantation, subjects will receive BUSULFAN intravenously (IV) via the Hickman line twice 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 help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

Arms

Assigned Interventions

Treatment Arm: Experimental

All patients treated with chemotherapy and transplantation.

Procedure: Stem Cell Transplant

The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains the 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, ATG

Prior to transplantation, subjects will receive BUSULFAN intravenously (IV) via the Hickman line twice 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 help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

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

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176917

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Masonic Cancer Center at the University of Minnesota ( Orchard, Paul J., MD )
Study ID Numbers:	0104M93821, MT1999-07
Study First Received:	September 12, 2005
Results First Received:	July 28, 2009
Last Updated:	July 28, 2009
ClinicalTrials.gov Identifier:	NCT00176917 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

stem cell transplant
storage disease
errors of metabolism

Study placed in the following topic categories:

I Cell Disease
Immunologic Factors
Methylprednisolone
Cyclophosphamide
Brain Diseases
Bone Diseases
Metabolism, Inborn Errors
Mucopolysaccharidoses
Mucopolysaccharidosis Type 6
Musculoskeletal Diseases
Connective Tissue Diseases
Brain Diseases, Metabolic, Inborn
Alkylating Agents
Metabolic Disorder
Deficiency Diseases

Alpha-Mannosidosis
Metabolic Diseases
Mucolipidoses
Lysosomal Storage Diseases
Mannosidase Deficiency Diseases
Central Nervous System Diseases
Bone Diseases, Metabolic
Immunosuppressive Agents
Mucopolysaccharidosis I
Antilymphocyte Serum
Genetic Diseases, Inborn
Busulfan
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Mucopolysaccharidosis VI

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Brain Diseases
Mucinoses
Bone Diseases
Metabolism, Inborn Errors
Mucopolysaccharidoses
Musculoskeletal Diseases
Therapeutic Uses
Connective Tissue Diseases
Brain Diseases, Metabolic, Inborn
Alkylating Agents

Alpha-Mannosidosis
Metabolic Diseases
Mucolipidoses
Lysosomal Storage Diseases, Nervous System
Lysosomal Storage Diseases
Mannosidase Deficiency Diseases
Nervous System Diseases
Central Nervous System Diseases
Bone Diseases, Metabolic
Immunosuppressive Agents
Pharmacologic Actions
Mucopolysaccharidosis I
Genetic Diseases, Inborn
Busulfan
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 10, 2009