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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT03910452
• Date of registration: 09/04/2019
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
• Scientific title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
• Date of first enrolment: October 28, 2019
• Target sample size: 30
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03910452
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Early Phase 1

Countries of recruitment

United States

Contacts

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

• Name: Elizabeth M Kang, M.D.

• Name: Elizabeth M Kang, M.D.
• Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)

Key inclusion & exclusion criteria

- 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 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.

EXCLUSION CRITERIA:

- 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
crea


Age minimum: 4 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Granulomatous Disease

Intervention(s)

Drug: Sirolimus

Drug: Busulfan

Drug: Cyclophosphamide

Biological: Allogeneic peripheral blood stem cell

Radiation: Total Body Irradiation

Drug: Alemtuzumab

Primary Outcome(s)

Engraftment - Chimerism [Time Frame: Day 30, 100, 6mo, 12 mo]

Secondary Outcome(s)

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]

Viral immune titrels [Time Frame: 6 mo, 1 year, 2 year, and 3 years post transplant.]

DHR as a marker of normal neutrophil function [Time Frame: Day 30, 100, 6 month and 1 year]

Secondary ID(s)

190080

19-I-0080

Source(s) of Monetary Support

Please refer to primary and secondary sponsors