Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease (CGD) With an Alemtuzumab, Busulfan and TBI-based Conditioning Regimen Combined With Cytokine (IL-6, +/- IFN-gamma) Antagonists

Summary

Background: Chronic granulomatous disease (CGD) affects the immune system. People with CGD are more likely to get infections. Drugs can help control infections, but these treatments can cause side effects including kidney failure and deafness. Stem cell transplants can cure CGD, but these don t always work. Objective: To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD. Eligibility: People aged 4-65 years with CGD. Design: Participants will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of their heart function and breathing. They will have imaging scans. They will have a bone marrow biopsy; a needle will be inserted into their hip to draw a sample of tissue from the bone. A tube called a catheter will be placed into a vein in the participant s chest. This catheter will remain in place for the transplant and recovery period. Blood for tests can be drawn from the catheter, and medications and the stem cells can be administered through it. Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant. They will get 2 doses of total body radiation on the same day. Participants will receive donor stem cells through the catheter. They will remain in the hospital for 6 weeks afterward. Participants will visit the clinic 2 to 3 times per week for 3 months after discharge. Follow-up visits will continue for 5 years.

Timeline

Start

2022-07-08

Primary completion

2032-12-31

Completion

2032-12-31

Publications

• Background Parta M, Kelly C, Kwatemaa N, Theobald N, Hilligoss D, Qin J, Kuhns DB, Zerbe C, Holland SM, Malech H, Kang EM. Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: a Single-Center Prospective Trial. J Clin Immunol. 2017 Aug;37(6):548-558. doi: 10.1007/s10875-017-0422-6. Epub 2017 Jul 28.
• Background Kadauke S, Myers RM, Li Y, Aplenc R, Baniewicz D, Barrett DM, Barz Leahy A, Callahan C, Dolan JG, Fitzgerald JC, Gladney W, Lacey SF, Liu H, Maude SL, McGuire R, Motley LS, Teachey DT, Wertheim GB, Wray L, DiNofia AM, Grupp SA. Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial. J Clin Oncol. 2021 Mar 10;39(8):920-930. doi: 10.1200/JCO.20.02477. Epub 2021 Jan 8.
• Background Chiesa R, Wang J, Blok HJ, Hazelaar S, Neven B, Moshous D, Schulz A, Hoenig M, Hauck F, Al Seraihy A, Gozdzik J, Ljungman P, Lindemans CA, Fernandes JF, Kalwak K, Strahm B, Schanz U, Sedlacek P, Sykora KW, Aksoylar S, Locatelli F, Stepensky P, Wynn R, Lum SH, Zecca M, Porta F, Taskinen M, Gibson B, Matthes S, Karakukcu M, Hauri-Hohl M, Veys P, Gennery AR, Lucchini G, Felber M, Albert MH, Balashov D, Lankester A, Gungor T, Slatter MA. Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults. Blood. 2020 Sep 3;136(10):1201-1211. doi: 10.1182/blood.2020005590.

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Indications