Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

Phase 2

Completed

• Conditions: Hurler Syndrome; Hunter Syndrome; Sly Syndrome; Alpha Mannosidosis; Krabbe Disease; Peroxisomal Disorders; Aspartylglucosaminuria; Sphingolipidoses; Adrenoleukodystrophy (ALD); Maroteaux-Lamy Syndrome
• Interventions: Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan; Procedure: Allogeneic stem cell transplantation; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil

• Registration Number: NCT01043640
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

Rationale: Chemotherapy administration before a donor stem cell transplant is necessary to stop the patient's immune system from rejecting the donor's stem cells. When healthy stem cells from a donor are infused into the patient, the donor white blood cells can provide the missing enzyme that causes the metabolic disease. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. This may be an effective treatment for inherited metabolic disorders.

Purpose: The design of this study is to achieve donor cell engraftment in patients with standard-risk inherited metabolic diseases with limited peri-transplant morbidity and mortality. This will be achieved through the administration of the chemotherapy regimen described. The intention is to follow transplanted patient for years after transplant monitoring them for complications of their disease and assisting families with a multifaceted interdisciplinary approach.

Detailed Description

Primary Objective:

* To estimate the proportion of patients with donor derived engraftment at day 100 post transplant as defined by 80% or greater donor cells in the CD3 (T cell) fraction

Secondary Objectives:

* To determine the incidence and severity of graft-versus-host disease (GVHD) by day 100

* To determine the incidence of peri-transplant mortality (death by day 100)

* To monitor donor cell chimerism at various time points following allogeneic transplantation with this transplant regimen as determined at day 28, 42, 100, 6 months and yearly for 5 years.

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2010-01-05
• Study First Submitted QC: 2010-01-06
• Study First Posted: 2010-01-07
• Primary Completion: 2015-06
• Results First Submitted: 2017-03-31
• Results First Submitted QC: 2017-03-31
• Results First Posted: 2017-05-12
• Study Completion: 2017-06
• Status Verified: 2017-09
• Last Update Submitted: 2018-01-09
• Last Update Posted: 2018-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Must have diagnosis of one of the following: mucopolysaccharidosis disorder, glycoprotein metabolic disorder, sphingolipidoses or inherited leukodystrophy, peroxisomal disorder or other inherited diseases of metabolism
• Must have an acceptable graft source as defined by University of Minnesota criteria
• Adequate organ function

Exclusion Criteria

• Pregnant - menstruating females must have a negative serum pregnancy test within 14 days of treatment start
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transplant Patients	Cyclosporine A	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Transplant Patients	Campath-1H	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Transplant Patients	Allogeneic stem cell transplantation	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Transplant Patients	Cyclophosphamide	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Transplant Patients	Busulfan	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Transplant Patients	Mycophenolate Mofetil	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Donor Derived Engraftment	Day 100 Post Transplant	Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4
Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4
Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4
Donor Cell Chimerism Following Transplant	One year	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4
Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4
Number of Patients Who Died Peri-Transplant	By Day 100 Post Transplant	Peri-transplant is defined as within 100 days of transplant.

Trial Locations

Locations (1)

Masonic Cancer Center, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States