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Protocol Details

Haploidentical Transplant for Patients with Chronic Granulomatous Disease (CGD) using Alemtuzumab, Busulfan and TBI with Post-Transplant Cyclophosphamide

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 4 Years
Max Age: 65 Years

Referral Letter Required


Population Exclusion(s)



Allogeneic Stem Cell Transplant;
Peripheral Blood Stem Cell Transplant;
Graft Versus Host Disease;
Non-Myeloablative Conditioning Regimen

Recruitment Keyword(s)



Chronic Granulomatous Disease

Investigational Drug(s)


Investigational Device(s)



Drug: Busulfan
Drug: Alemtuzumab
Drug: Cyclophosphamide
Drug: Sirolimus
Radiation: Total Body Irradiation
Biological/Vaccine: Allogeneic peripheral blood stem cell

Supporting Site

National Institute of Allergy and Infectious Diseases


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:

Medical history

Physical exam

Blood tests

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.

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-Must have sufficient complications from underlying disease to warrant undergoing transplantation. (History of one or more life threatening infections and/or an ongoing infection not responsive to current medical therapy and/or ongoing inflammation along with an oxidase level within quartile 1 or 2.

-Patients will be reviewed at a multidisciplinary meeting for assessment of the risk/benefit ratio of transplant for the patient to determine suitability for this high risk treatment. This multidisciplinary meeting is a combined NCI/NIAID bimonthly meeting comprised of investigators from multiple branches of the NC and NIAID to review patients with immunodeficiencies being considered for various transplant protocols.

-Patients who are deemed to have colitis in the severe category (severe colitis) as defined below in the Subject Exclusion Criteria, who are at high risk for GvHD, will be included in enrollment to the protocol after 10 patients have completed the protocol regimen successfully. Patients among the first 10 may have colitis that is not deemed in the severe category. The success of the regimen will be determined as engraftment with a maximum GvHD of grade 2 (See the exclusion criteria for patients with severe colitis).

- Patients who are 4 65 years of age.

- HLA mismatched related (more than 1 mismatch) donor graft available.

- Ability to comprehend and willingness to sign the informed consent or have a parent/guardian consent if the donor is a minor; assent being obtained from minors as appropriate.

- Must be HIV negative.

- Must be able to stay within one hour s travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post-transplant period.

-Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance with NIH Form-200 NIH Durable Power of Attorney for Health Care Decision Making."

- Where appropriate, subjects must agree to use contraception for 3 months post-transplant.

NOTE: Alemtuzumab (IV formulation) is no longer distributed commercially. In order to receive product, the physician must contact the program for the patient. If the subject is not willing to consent to submit their info (address, date of birth and gender) to the program such that we can obtain the drug, then we cannot proceed with conditioning therefore no transplant will occur on this protocol.

Participation of Women:

Contraception: The effects of the combination of conditioning medications (alemtuzumab, busulfan, cyclophosphamide and mycophenolate mofetil) and total body irradiation on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post transplant. Females of childbearing-age must have a negative pregnancy test result prior to receiving any chemotherapy or conditioning agents. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately.

Participation of Children:

Children greater than or equal to 4 years of age may participate in this study.


- The subject cannot have a 9/10 or 10/10 HLA matched related or unrelated donor.

- Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater than or equal to 3

- Patients with inflammatory bowel disease deemed in the severe category (severe colitis), because they are at higher risk for GvHD, will be excluded from the protocol until there are 10 patients without severe colitis that have successfully completed a regimen, as determined by engraftment and acute GvHD of a maximum of grade 2. Severity of colitis will be determined in consultation with a gastroenterologist specialist. However, severe colitis will be evaluated within 4 months of transplant and defined as any of the following (where this screening may be performed on a natural history or screening protocol):

-- The consultant gastroenterologist clinically determines that the patient has severe colitis.

-- Patient adult CDAI score is in the 350-450 range and Pediatric CDAI score is greater than 30 within the month before initiation of conditioning Crohn s Disease Activity Index (CDAI) for transplant.

-- The patient has been requiring 1 mg/kg/day or more of prednisone or equivalent steroid for control of colitis within 1 month of the CDAI scoring used to determine eligibility.

-- The patient requires continuing treatment with a biologic that consists of anti-TNF alpha (e.g. infliximab, Humira, certolizumab and others of this family), anti-interleukin 12 (e.g. Ustekinumab) or anti-integrin (e.g. Vedolizumab) for control of colitis within 2 months of the CDAI scoring used to determine eligibility.

-- If the patient had a colonoscopy within 6 months of transplant which revealed findings of a simplified endoscopic score of Crohn s Disease (SES-CD) greater than 15.

- Left ventricular ejection fraction < 40%.

- Transaminases > 5x upper limit of normal.

- Psychiatric disorder or mental deficiency severe enough as to make compliance with the HSCT treatment unlikely, and/or making regulatorily and legally effective informed consent impossible. This will include adult patients that are unable to consent.

- Major anticipated illness or organ failure incompatible with survival from AlloPBSC transplant.

- Pregnant or lactating.

- HIV positive.

- Participants older than 65 are excluded. It is known from standard transplantation that these participants have a higher risk of morbidity and mortality related to transplantation. Given the investigational nature of this protocol, the risk benefit ratio is not warranted to include these participants at this time.

- Participants who are not willing to submit their information as part of the alemtuzumab (Campath ) Distribution Program application or participants whom the Distribution Program committee has determined are not qualified to receive alemtuzumab.

- Any condition or circumstance, which the Principal Investigator (PI) feels, would create difficulty in maintaining compliance with the requirements of this protocol.

- Any active infectious disease, whether CGD-related or not, that is deemed to be incompatible with successful tolerance to the rigors of transplantation.

- C-reactive protein of greater than 100 Units within 6 weeks of anticipated transplant.

-Any history of seizures, controlled or otherwise, if unrelated to an infectious cause.

-Any history of any neurologic disorders or family history of such, unrelated to infection.

-Brain CT or MRI findings suggestive of neurologic disorders other than infection.

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Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M, Kumar A, Jodele S, Myers KC, Chandra S, Leemhuis T, Mehta PA, Bleesing JJ, Davies SM, Jordan MB, Filipovich AH. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transplant. 2013 Nov;19(11):1625-31. doi: 10.1016/j.bbmt.2013.09.001. Epub 2013 Sep 10.

Munchel A, Kesserwan C, Symons HJ, Luznik L, Kasamon YL, Jones RJ, Fuchs EJ. Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. Pediatr Rep. 2011 Jun 22;3 Suppl 2:e15. doi: 10.4081/pr.2011.s2.e15.

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.

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Principal Investigator

Referral Contact

For more information:

Elizabeth M. Kang, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CRC BG RM 6-3750
(301) 402-7567

Elizabeth M. Kang, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CRC BG RM 6-3750
(301) 402-7567

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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