Stem Cell Transplantation for Hurler

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00176917
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Duration (Months): 132
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mannosidosis; Mucolipidosis Type II (I-cell Disease)	Procedure: Stem Cell Transplant; Drug: Busulfan, Cyclophosphamide, ATG	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)
• Study Start Date: May 1, 1999
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Percentage of Donor Cells in Study Population (Chimerism). [at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year]

   Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).

Secondary Outcome Measures

1. Number of Patients Surviving on Study [at 100 days, 1 year, and 3 years post transplant]

   Number of patients surviving (alive) at specified timepoints.

2. Number of Patients Who Failed Engraftment. [Day 42 Post Transplant]

   Toxicity (undesireable effect) of hematologic donor cell engraftment is determined by failure to engraft at Day 42.

3. Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD). [Day 100 Post Transplant]

   Toxicity (undesireable effect) of this stem cell transplant preparative regimen due to acute graft-versus-host disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00176917
• Other Study ID Numbers: UMN-MT1999-07; 0104M93821; NCT00005899
• First Posted: Sep 15, 2005
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: stem cell transplant; storage disease; errors of metabolism
• Additional relevant MeSH terms: Mucolipidoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mannosidase Deficiency Diseases; alpha-Mannosidosis; Mucopolysaccharidosis VI; Cyclophosphamide; Busulfan; Thymoglobulin

Study Results

Participant Flow

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Period Title: Overall Study
STARTED	41
COMPLETED	41
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Overall Participants	41
Age (Count of Participants)
<=18 years	41 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	1.8 (1.4)
Sex: Female, Male (Count of Participants)
Female	23 56.1%
Male	18 43.9%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Mean Percentage of Donor Cells in Study Population (Chimerism).
Description	Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).
Time Frame	at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year

Outcome Measure Data

Analysis Population Description

Day 21 (24 patients included), Day 42 (15 pts), Day 60 (29 pts), Day 100 (25 pts), 6 Months (18 pts), 1 Year (16 pts).

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Measure Participants	41
21 Days Post Transplant	85.8 (28.4)
42 Days Post Transplant	73.2 (31.6)
60 Days Post Transplant	84.6 (27.9)
100 Days Post Transplant	81.1 (26.8)
6 Months Post Transplant	81.6 (29.6)
1 Year Post Transplant	91.5 (18.8)

2. Secondary Outcome

Title	Number of Patients Surviving on Study
Description	Number of patients surviving (alive) at specified timepoints.
Time Frame	at 100 days, 1 year, and 3 years post transplant

Outcome Measure Data

Analysis Population Description

Day 100 and 1 Year timepoints include all 41 patients. Year 3 includes 36 patients (5 pts not yet at followup timepoint.)

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Measure Participants	41
Day 100 Post Transplant	37 90.2%
1 Year Post Transplant	28 68.3%
3 Years Post Transplant	27 65.9%

3. Secondary Outcome

Title	Number of Patients Who Failed Engraftment.
Description	Toxicity (undesireable effect) of hematologic donor cell engraftment is determined by failure to engraft at Day 42.
Time Frame	Day 42 Post Transplant

Outcome Measure Data

Analysis Population Description

1 patient of 41 failed engraftment - per protocol.

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Measure Participants	41
Number [Participants]	1 2.4%

4. Secondary Outcome

Title	Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).
Description	Toxicity (undesireable effect) of this stem cell transplant preparative regimen due to acute graft-versus-host disease.
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
Measure Participants	41
Number [Participants]	2 4.9%

Adverse Events

Arm/Group Title	Transplant Patients
Arm/Group Description	Patients that received hematopoietic stem cell transplant.
All Cause Mortality
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	0/41 (0%)
Other (Not Including Serious) Adverse Events
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	0/41 (0%)

Limitations/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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.