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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease

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. 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 ca

Detailed Summary:

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 mo
Sponsor: Baylor College of Medicine

Current Primary Outcome: 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.


Original Primary Outcome:

  • Treat patients with Chronic Granulomatous Disease refractory to conventional therapy and without a HLA matched sibling donor by performing stem cell transplantation from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors. [ Time Frame: 120 days ]
  • Estimate engraftment rate [ Time Frame: 120 days ]
  • To estimate 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 ]
  • To examine the potential for reversal of organ toxicity (e.g. lung, liver, intestine) following engraftment and stable normal neutrophil function. [ Time Frame: 120 days ]


Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

Information By: Baylor College of Medicine

Dates:
Date Received: December 19, 2007
Date Started: March 2004
Date Completion: July 2018
Last Updated: January 20, 2017
Last Verified: January 2017