Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
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|ClinicalTrials.gov Identifier: NCT03910452|
Recruitment Status : Recruiting
First Posted : April 10, 2019
Last Update Posted : July 19, 2022
CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor.
To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant.
People ages 4-65 with CGD for whom stem cell transplant may be a cure and who do not have a perfectly matched donor, related or unrelated.
Participants will be screened with:
Participants will be admitted to the hospital about 2 weeks before the transplant. They will have blood, urine, breathing, and heart tests. They may have CT and/or MRI scans. They will have a needle inserted into their hipbone to remove marrow. They will have dental, neurologic, and psychologic tests. They will have a central catheter placed: A line will be placed into a vein in their upper chest. They will get drugs, chemotherapy, and radiation to prepare for the transplant.
Participants will receive the donated cells through their catheter. The cells will be from one of their relatives.
Participants will stay in the hospital about 6 weeks after the transplant.
After they leave the hospital, participants will have to stay in the area with visits about 2 times a week for approximately 100 days post transplant. Then visits will be every 3 to 6 months for 2 years. Then visits will be once a year.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Granulomatous Disease||Drug: Busulfan Drug: Alemtuzumab Drug: Cyclophosphamide Drug: Sirolimus Radiation: Total Body Irradiation Biological: Allogeneic peripheral blood stem cell||Early Phase 1|
Allogeneic transplant using human leukocyte antigen (HLA) matched donors, both related and unrelated, has proven curative for patients with various immunodeficiencies, including those with ongoing infections. However, donor availability remains a limiting factor in the application of this treatment modality. For this protocol, a haploidentical donor is a related donor with more than 1 HLA antigen mismatch. The use of haploidentical related donors has in the past been fraught with a greater rate of complications related to both higher rates of graft versus host disease (GvHD) and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a reduced intensity novel conditioning regimen using alemtuzumab, targeted busulfan, and low dose total body irradiation (see schema below) followed by post-transplant cyclophosphamide for patients with chronic granulomatous disease (CGD) who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality. However, patients with CGD have high rates of Crohn s Disease-like inflammatory bowel disease, predominantly colitis, where uncontrolled severe IBD may increase risk of GvHD. For this reason, the first 10 patients enrolled will exclude those deemed to have intestinal inflammation in the severe category.
As part of the study design, the protocol will enroll patients sequentially.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide|
|Actual Study Start Date :||October 28, 2019|
|Estimated Primary Completion Date :||June 15, 2034|
|Estimated Study Completion Date :||June 15, 2034|
This is a single arm open-label pilot study.
3 days of IV Busulfan. An alkylating chemotherapeutic agent determined to have broad myelosuppressive effects. On this study is being used as part of conditioning regimen for myelosuppressive properties as per package insert and standard of care.
5 days of IV Alemtuzumab. A humanized monoclonal antibody directed against CD52 (which is abundantly expressed on all human lymphocytes), and causes T cell activation in vitro as well as complement-mediated lysis and antibody-dependent cellular toxicity. For this study, being used as part of the conditioning regimen per package insert and standard of practice.
2 days of IV Cyclophosphamide. This is an antineoplastic, and for this study is bine used for its immunosuppressive mechanism of action per package insert and standard of care
Post Peripheral blood stem cell infusion. It is used for its immunosuppressive mechanism of action.
Radiation: Total Body Irradiation
2 fractionated doses on -2 day. It is used for its immunosuppressive mechanism of action. It is SOP for conditioning for transplant.
Biological: Allogeneic peripheral blood stem cell
IV infused donor peripheral blood stem cell. Stem cells are cells that give rise to the blood cells - red blood cells that carry oxygen, white blood cells that help the body to fight infections, and platelets that help make the blood clot. Collected and infused per the standard of operating procedures established by the Department of Transfusion Medicine.
- Engraftment - Chimerism [ Time Frame: Day 30, 100, 6mo, 12 mo ]Myeloid chimerism >50% without incurring grade 3 steroid refractory or any grade 4 acute graft versus host disease or severe extensive chronic graft versus host disease post transplant.
- Viral immune titrels [ Time Frame: 6 mo, 1 year, 2 year, and 3 years post transplant. ]Viral Immune Reconstitution using viral reactivation as a marker.
- Overall Survival/Event-Free survival [ Time Frame: continuous observation/Day +14, 30, 60, 100, 6 mo, 12 mo, 18 mo, 2,3,4,5 years ]3) Assessment of rates of Overall Survival and Event Free Survival (event being late graft loss or recurrence of CGD phenotype).
- DHR as a marker of normal neutrophil function [ Time Frame: Day 30, 100, 6 month and 1 year ]1) Myeloid immune reconstitution levels with DHR as a marker of normal neutrophil function by 1-year post transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03910452
|Contact: Corin Kelly, R.N.||(301) firstname.lastname@example.org|
|Contact: Elizabeth M Kang, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Elizabeth M Kang, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|