Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

  • End date
    Jun 15, 2034
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 4 April 2023
stem cell transplantation
graft versus host disease
bone marrow transplant
blood test



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.


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.

Condition Chronic Granulomatous Disease
Treatment cyclophosphamide, busulfan, Total body irradiation, Sirolimus, alemtuzumab, Allogeneic peripheral blood stem cell
Clinical Study IdentifierNCT03910452
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on4 April 2023


Yes No Not Sure

Inclusion Criteria

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 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 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 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 to 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

Exclusion Criteria

Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater
The subject cannot have a 9/10 or 10/10 HLA matched related or unrelated donor
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
Left ventricular ejection fraction < 40%
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
Pregnant or lactating
greater than 30 within the month before initiation of conditioning Crohn s
HIV positive
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)
C-reactive protein of greater than 100 Units within 6 weeks of anticipated transplant
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
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
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
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
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
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
Brain CT or MRI findings suggestive of neurologic disorders other than infection
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