Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01043640
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arm: 1
• Duration (Months): 90
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders	Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan; Procedure: Allogeneic stem cell transplantation; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Transplant Patients Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.

Drug: Campath-1H; Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV); Other Names: Alemtuzumab ; Drug: Cyclophosphamide; Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.; Other Names: Cytoxan(R) ; Drug: Busulfan; Administered every 6 hours: If < or = 12 kg then 1.1 mg/kg/dose intravenous (IV). If > 12 kg then 0.8 mg/kg/dose IV; Other Names: Busulfex(R) ; Procedure: Allogeneic stem cell transplantation; Administered > 24 hours after last dose of busulfan.; Other Names: stem cell transplant ; Drug: Cyclosporine A; 2.5 mg/kg/dose intravenous (IV_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight: If body weight is ≤ 40 kg dosing will be 3 times daily If body weight is > 40 kg dosing will be 2 times daily An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2 times the current IV dose (maximum 12.5 mg/kg/day as initial oral dose).; Other Names: CsA ; Drug: Mycophenolate Mofetil; 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: The same dosage is used orally or intravenously. Stop MMF at day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.; Other Names: MMF

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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

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

5. 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

6. Number of Patients Who Died Peri-Transplant [By Day 100 Post Transplant]

   Peri-transplant is defined as within 100 days of transplant.

7. Donor Cell Chimerism Following Transplant [Day 28]

   Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

8. Donor Cell Chimerism Following Transplant [Day 42]

   Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

9. Donor Cell Chimerism Following Transplant [Day 100]

   Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

10. Donor Cell Chimerism Following Transplant [6 months]

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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: NCT01043640
• Other Study ID Numbers: 2009LS088; MT2009-19
• First Posted: Jan 7, 2010
• Last Update Posted: Feb 5, 2018
• Last Verified: Sep 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: inherited metabolic disorders
• Additional relevant MeSH terms: Adrenoleukodystrophy; Mucopolysaccharidosis II; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; Sphingolipidoses; Fucosidosis; Mucopolysaccharidoses; Mannosidase Deficiency Diseases; alpha-Mannosidosis; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Peroxisomal Disorders; Mucopolysaccharidosis VII; Aspartylglucosaminuria; Metabolic Diseases; Disease; Syndrome; Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Busulfan; Alemtuzumab; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Period Title: Overall Study
STARTED	46
COMPLETED	46
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Overall Participants	46
Age (Count of Participants)
<=18 years	46 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	11 23.9%
Male	35 76.1%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	42 91.3%

2. Secondary Outcome

Title	Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)
Description	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
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	32 69.6%

3. Secondary Outcome

Title	Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)
Description	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
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	2 4.3%

4. Secondary Outcome

Title	Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)
Description	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
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	5 10.9%

5. Secondary Outcome

Title	Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)
Description	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
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	2 4.3%

6. Secondary Outcome

Title	Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)
Description	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
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	5 10.9%

7. Secondary Outcome

Title	Number of Patients Who Died Peri-Transplant
Description	Peri-transplant is defined as within 100 days of transplant.
Time Frame	By Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Count of Participants [Participants]	2 4.3%

8. Secondary Outcome

Title	Donor Cell Chimerism Following Transplant
Description	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Mean (Standard Deviation) [percentage of donor cells]	95 (9)

9. Secondary Outcome

Title	Donor Cell Chimerism Following Transplant
Description	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Mean (Standard Deviation) [percentage of donor cells]	93 (15)

10. Secondary Outcome

Title	Donor Cell Chimerism Following Transplant
Description	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Mean (Standard Deviation) [percentage of donor cells]	90 (26)

11. Secondary Outcome

Title	Donor Cell Chimerism Following Transplant
Description	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Mean (Standard Deviation) [percentage of donor cells]	94 (22)

12. Secondary Outcome

Title	Donor Cell Chimerism Following Transplant
Description	Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Measure Participants	46
Mean (Standard Deviation) [percentage of donor cells]	99 (4)

Adverse Events

Arm/Group Title	Transplant Patients
Arm/Group Description	Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Campath-1H: Days -21, -20 and -19, 0.3 mg/kg SQ or IV Cyclophosphamide: Days -10 through -6, 50 mg/kg/day IV with Mesna Busulfan: Days -5 through Day -2, 1.1 mg/kg/dose IV if ≤ 12 kg; 0.8 mg/kg/dose IV if > 12 kg Allogeneic stem cell transplantation: > 24 hours after last dose of busulfan Cyclosporine A: 2.5 mg/kg/dose IV beginning on day -3. Dosing will be 3 times daily if body weight is ≤ 40 kg and 2 times daily if body weight is > 40 kg Mycophenolate Mofetil: 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: Stop MMF at Day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
All Cause Mortality
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	8/46 (17.4%)
Cardiac disorders
Pericardial Effusion	2/46 (4.3%)
Cardiac Arrest	1/46 (2.2%)
Gastrointestinal disorders
Diarrhea	2/46 (4.3%)
Nervous system disorders
Intracerebral Hemorrhage	1/46 (2.2%)
Renal and urinary disorders
Renal Failure	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/46 (2.2%)
Pulmonary Veno-Occlusive Disease	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Transplant Patients
	Affected / at Risk (%)	# Events
Total	40/46 (87%)
Cardiac disorders
Pericardial Effusion	7/46 (15.2%)
Tachycardia	3/46 (6.5%)
Gastrointestinal disorders
Diarrhea	4/46 (8.7%)
Hemorrhage, Gastrointestinal	8/46 (17.4%)
Mucositis	11/46 (23.9%)
Nausea	6/46 (13%)
Vomiting	4/46 (8.7%)
General disorders
Fever	11/46 (23.9%)
Graft Versus Host Disease	9/46 (19.6%)
Infections and infestations
Infection, NOS	35/46 (76.1%)
Infection, Respiratory	9/46 (19.6%)
Infection, Gastrointestinal	7/46 (15.2%)
Investigations
Bilirubin Increased	16/46 (34.8%)
Metabolism and nutrition disorders
Anorexia	7/46 (15.2%)
Nervous system disorders
Headache	3/46 (6.5%)
Renal and urinary disorders
Hemorrhage, Genitourinary	10/46 (21.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	14/46 (30.4%)
Hypoxia	14/46 (30.4%)
Skin and subcutaneous tissue disorders
Hives	3/46 (6.5%)
Rash	10/46 (21.7%)
Vascular disorders
Hypertension	21/46 (45.7%)
Hypotension	3/46 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.