Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease (MUNCHR)
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. The course over time of CGD may differ in severity among patients, but those children who develop severe infection at a young age are most likely to have a more severe clinical course. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment with these medications, most patients with CGD will have chronic and recurrent infections. Transfusion of healthy or normal 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 such as the lung, liver, or bone. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs such as the kidney. 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 transferred or transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy brother or sister 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 making the donor's white cells. 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 an unrelated donor. The donor will be closely matched to the patients immune type but the donor is not a brother or sister. This type of transplantation has been done only a few times for patients with CGD, although this type of transplant is commonly done for other reasons, e.g. leukemia. 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.
|Chronic Granulomatous Disease||Drug: Busulfan Biological: Alemtuzumab Drug: Cyclophosphamide Drug: Fludarabine Drug: Cyclosporine Procedure: Stem Cell Infusion||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease|
- Number of patients that have engraftment after transplant. [ Time Frame: 120 days ]To estimate the engraftment rate and 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.
- Estimating the risk for acute and chronic GVHD and regimen related morbidity/mortality for patients with CGD following 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 ]
- Examining the potential for reversal of organ toxicity (e.g. lung, liver, intestine) following engraftment and stable normal neutrophil function. [ Time Frame: 120 days ]
|Study Start Date:||March 2004|
|Estimated Study Completion Date:||July 2018|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
Experimental: Allogeneic unrelated transplant
Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion.
Days -9 through -6
1 mg/kg initially (based on weight)
Other Name: BusulfexBiological: Alemtuzumab
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
Other Name: CampathDrug: Cyclophosphamide
Days -5 through -2
Other Name: CytoxanDrug: Fludarabine
Day -5 through Day -2
Other Name: FludaraDrug: Cyclosporine
Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.
Other Name: SandimmuneProcedure: Stem Cell Infusion
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00578643
|Contact: Robert Krance, MDemail@example.com|
|Contact: Marlen Dinufirstname.lastname@example.org|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Robert Krance, MD 832-824-4661 email@example.com|
|Contact: Marlen Dinu 832-824-4881 firstname.lastname@example.org|
|Principal Investigator:||Robert Krance, MD||Baylor College of Medicine|