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Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease (MUNCHR)

Primary Purpose

Chronic Granulomatous Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Busulfan
Alemtuzumab
Cyclophosphamide
Fludarabine
Cyclosporine
Stem Cell Infusion
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Granulomatous Disease focused on measuring Stem Cell Transplant, Chronic Granulomatous Disease, Fludarabine, Busulfan, Cyclophosphamide

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH enzyme mutation confirmed by genetic analysis with abnormal NBT.

Patients must not have an HLA genotype identical donor.

Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA phenotype-matched related donor.

Patients must have had at least one serious infection characteristic of those manifested in patients with CGD.

Patients must not have active infection. An active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part).

No cumulative organ dysfunction that, in the estimation of the treating physicians, will diminish the patient's likelihood to survive this procedure.

Negative pregnancy test for post-pubertal female patients.

Echocardiogram shortening fraction >/= 28%.

DLCO 50% or greater predicted or FEV1 >/= 50% predicted.

EXCLUSION CRITERIA:

Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis).

Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline.

Invasive bone or bone marrow disease.

Lack of potential hematologic blood product donors in the past (related to McLeod phenotype).

Sites / Locations

  • Texas Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic unrelated transplant

Arm Description

Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion.

Outcomes

Primary Outcome Measures

Percentage of Participants With Engraftment
To estimate the engraftment rate for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.

Secondary Outcome Measures

Number of Patients That Have Complete Donor Chimerism After Transplant.
To estimate the likelihood of complete donor chimerism for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
Number of Patients That Have Acute GVHD and Regimen Related Morbidity/Mortality Post Transplant.
To estimate the risk for acute GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.
Number of Patients That Have Chronic GVHD and Regimen Related Morbidity/Mortality Post Transplant.
To estimate the risk for chronic GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.

Full Information

First Posted
December 19, 2007
Last Updated
October 11, 2018
Sponsor
Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00578643
Brief Title
Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
Acronym
MUNCHR
Official Title
HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
July 31, 2017 (Actual)
Study Completion Date
November 24, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. This condition cannot presently be cured by standard treatment with drugs or surgery. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment, most patients with CGD will have chronic and recurrent infections. Transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs too. Infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly. It is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy sibling and who share the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. These healthy white cells can fight infection and prevent future infections for a patient with CGD. Patients on this study will receive stem cells from a related or unrelated donor. The donor will be closely matched to the patient's immune type but the donor is not a sibling. The reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. It is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. It is possible that the side-effects of treatment may be too severe so that the transplant won't work. The purpose of this research study is to evaluate whether or not patients with CGD treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.
Detailed Description
In order to transplant stem cells we will need to give the patient drugs or high-dose chemotherapy to kill or destroy most of the blood forming and immune cells in the bone marrow. This is necessary to allow the donor stem cells to live and grow (engraft) in the bone marrow space. After the drug treatment is completed, the patient will be given the stem cells from the donor. The drug treatment is as follows: Day -9 Busulfan Day -8 Busulfan Day -7 Busulfan Day -6 Busulfan Day -5 Alemtuzumab, Fludarabine, Cyclophosphamide Day -4 Alemtuzumab, Fludarabine, Cyclophosphamide Day -3 Alemtuzumab, Fludarabine, Cyclophosphamide Day -2 Alemtuzumab, Fludarabine, Cyclosporine, Cyclophosphamide Day -1 REST Day 0 Stem cell infusion The day after the chemotherapy treatment is completed, the patient will receive the healthy stem cells by vein, like a blood transfusion. Once in the bloodstream, the marrow cells will go to the bone marrow and grow. It is also possible that if the marrow takes, it will cause a disease known as graft-versus-host disease (GVHD). To prevent GVHD, we will give the patient cyclosporine and Methotrexate. Methotrexate will be administered on Days 1, 3, 6 and 11 after the transplant. The cyclosporine therapy will continue for a longer period of time, however if the patient does not develop GVHD, it will be discontinued by 6 months after the stem cell transplant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Granulomatous Disease
Keywords
Stem Cell Transplant, Chronic Granulomatous Disease, Fludarabine, Busulfan, Cyclophosphamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic unrelated transplant
Arm Type
Experimental
Arm Description
Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
Days -9 through -6 1 mg/kg initially (based on weight)
Intervention Type
Biological
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Campath
Intervention Description
Day -5 through Day -2 Dose is based on weight: Less than 15 kg: 3 mg More than 15 kg to 30 kg: 5 mg More than 30 kg: 15 mg
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Days -5 through -2 50 mg/kg
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Day -5 through Day -2 30 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
Sandimmune
Intervention Description
Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Infusion
Intervention Description
Stem Cell: Either bone marrow, cord blood, or peripheral blood stem cells may be used for stem cell transplantation. It is desired to infuse: for bone marrow, nucleated cells ≥ 4 X 10^8/kg recipient weight; for cord blood ≥ 3 X 10^7/kg nucleated cells; for peripheral blood stem cells ≥ 1 X 10^/kg CD34+ cells.
Primary Outcome Measure Information:
Title
Percentage of Participants With Engraftment
Description
To estimate the engraftment rate for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
Time Frame
28 days post transplant
Secondary Outcome Measure Information:
Title
Number of Patients That Have Complete Donor Chimerism After Transplant.
Description
To estimate the likelihood of complete donor chimerism for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.
Time Frame
120 days post transplant
Title
Number of Patients That Have Acute GVHD and Regimen Related Morbidity/Mortality Post Transplant.
Description
To estimate the risk for acute GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.
Time Frame
Assessed between day 0 and day 100 post transplant
Title
Number of Patients That Have Chronic GVHD and Regimen Related Morbidity/Mortality Post Transplant.
Description
To estimate the risk for chronic GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.
Time Frame
Assessed between day 100 and day 365 post transplant

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH enzyme mutation confirmed by genetic analysis with abnormal NBT. Patients must not have an HLA genotype identical donor. Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA phenotype-matched related donor. Patients must have had at least one serious infection characteristic of those manifested in patients with CGD. Patients must not have active infection. An active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part). No cumulative organ dysfunction that, in the estimation of the treating physicians, will diminish the patient's likelihood to survive this procedure. Negative pregnancy test for post-pubertal female patients. Echocardiogram shortening fraction >/= 28%. DLCO 50% or greater predicted or FEV1 >/= 50% predicted. EXCLUSION CRITERIA: Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis). Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline. Invasive bone or bone marrow disease. Lack of potential hematologic blood product donors in the past (related to McLeod phenotype).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Krance, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease

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