Stem Cell Transplantation for Hurler

NCT ID: NCT00176917

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-05-31
• Study Completion Date: 2010-05-31

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.

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mannosidosis; Mucolipidosis Type II (I-cell Disease)

Keywords

stem cell transplant; storage disease; errors of metabolism

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

All patients treated with chemotherapy and transplantation.

Group Type: EXPERIMENTAL

Stem Cell Transplant

Intervention Type: PROCEDURE

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).

Busulfan, Cyclophosphamide, ATG

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Other Intervention Names

Bone Marrow Transplant; Busulfex, Cytoxan, Thymoglobulin

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Orchard, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

0104M93821

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-MT1999-07

Identifier Type: -

Identifier Source: org_study_id

NCT00005899

Identifier Type: -

Identifier Source: nct_alias