Stem Cell Transplantation for Hurler

December 3, 2017 updated by: Masonic Cancer Center, University of Minnesota

Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm
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).
Other Names:
  • Bone Marrow Transplant
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.
Other Names:
  • Busulfex, Cytoxan, Thymoglobulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).
at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Surviving on Study
Time Frame: at 100 days, 1 year, and 3 years post transplant
Number of patients surviving (alive) at specified timepoints.
at 100 days, 1 year, and 3 years post transplant
Number of Patients Who Failed Engraftment.
Time Frame: Day 42 Post Transplant
Toxicity (undesireable effect) of hematologic donor cell engraftment is determined by failure to engraft at Day 42.
Day 42 Post Transplant
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).
Time Frame: Day 100 Post Transplant
Toxicity (undesireable effect) of this stem cell transplant preparative regimen due to acute graft-versus-host disease.
Day 100 Post Transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1999

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Actual)

December 28, 2017

Last Update Submitted That Met QC Criteria

December 3, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMN-MT1999-07
  • 0104M93821 (Other Identifier: IRB, University of Minnesota)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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