Stem Cell Transplantation for Hurler

NCT00176917 | Completed Phase 2 Results

• 2 other identifiers: UMN-MT1999-070104M93821
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

stem cell transplant; storage disease; errors of metabolism

Outcome Measures

Primary Outcomes (1)

• Mean Percentage of Donor Cells in Study Population (Chimerism).

  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 Outcomes (3)

• Number of Patients Surviving on Study

  at 100 days, 1 year, and 3 years post transplant

• Number of Patients Who Failed Engraftment.

  Day 42 Post Transplant

• Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).

  Day 100 Post Transplant

Study Arms (1)

Treatment Arm

EXPERIMENTAL

All patients treated with chemotherapy and transplantation.

Procedure: Stem Cell Transplant; Drug: Busulfan, Cyclophosphamide, ATG

Interventions

Stem Cell Transplant 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).

Also known as: Bone Marrow Transplant

Treatment Arm

Busulfan, Cyclophosphamide, ATG 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.

Also known as: Busulfex, Cytoxan, Thymoglobulin

Treatment Arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mannosidase Deficiency Diseases; Mucolipidoses

Interventions

Stem Cell Transplantation; Bone Marrow Transplantation; Busulfan; Cyclophosphamide; thymoglobulin

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Based on variability in age, diagnosis and condition of these patients, the data on enzyme levels and neuropsych testing is extremely difficult to report. See Secondary Outcome Measures #3 and #4; no other adverse events were collected.

Results Point of Contact

• Title: Paul J. Orchard, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

orcha001@umn.edu

612-626-2313

Study Officials

• Paul Orchard, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: May 1, 1999
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: September 4, 2009

Record last verified: 2017-12

Locations

US (1)