Overview

Matched Related and Unrelated Donor Stem Cell Transplantation for Severe Combined Immune Deficiency (SCID): Busulfan-based Conditioning With h-ATG, Radiation, and Sirolimus

Status:
Enrolling by invitation
Trial end date:
2026-09-09
Target enrollment:
0
Participant gender:
All
Summary
Background: Severe combined immune deficiency (SCID) is a group of conditions where the immune system does not work properly. The only cure for most SCIDs is a stem cell transplant (getting cells from a donor). These transplants can have serious complications. Before the transplant, people often get high doses of drugs and radiation to prepare the body to accept the cells from the donor. Researchers want to see if low doses of drugs alone without radiation work just as well as low doses of drugs with radiation for SCID patients getting stem cell transplants. Objective: To test a set of drugs with or without radiation given before a stem cell transplant. Eligibility: People ages 3-40 who have SCID and who have a stem cell donor - either related or unrelated. Design: Participants will be admitted to the hospital 10 days before transplant. They will undergo: medical history medication review physical exam blood and urine tests (may include a 24-hour urine collection) heart, lung, and breathing tests imaging scans bone marrow sample nutrition assessment dental exam eye exam meeting with a social worker. Participants will get a plastic port called a central line. It is a hollow tube that is placed in the upper chest. It will be used to give medicines and take blood. All participants will take chemotherapy drugs. Some will get radiation. Participants will have a stem cell transplant. They will get the cells as an infusion through their central line. They will stay in the hospital for 30 days after transplant. Participants must stay within 1 hour of NIH for 3 months after transplant. During this time, they will have follow-up visits at NIH at least once a week. Then they will have follow-up visits once or twice a year for 5-6 years.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Treatments:
Busulfan
Sirolimus
Criteria
- INCLUSION CRITERIA:

- Must have confirmed genetic diagnosis of SCID (gamma c or JAK3 deficiency) by
identification of a mutation in the responsible genes or by demonstrating failure to
detect gamma c or JAK3 in immune blood cells (as in the case of patients who have been
treated but now have waning immunity).

- Must have either evidence of waning immunity by T cell analysis, and/or sufficient
complications from underlying disease to warrant undergoing transplantation as defined
as meeting greater than or equal to1 of the following clinical criteria:

i- Infections (not including molluscum, warts, or mucocutaneous candidiasis; see vii
and viii below): 3 significant new or chronic active infections during the 2 years
preceding evaluation for enrollment, with each infection accounting for one criterion.

Infections are defined as an objective sign of infection (fever >38.3 (Infinite)C [101
degrees F] or neutrophilia or pain/redness/swelling or radiologic/ultrasound imaging
evidence or typical lesion or histology or new severe diarrhea or cough with sputum
production). In addition to one or more of these signs/symptoms of possible infection,
there also must be at least 1 of the following criteria as evidence of the attending
physician s intent to treat a significant infection (a and b) or objective evidence for a
specific pathogen causing the infection (c):

1. Treatment (not prophylaxis) with systemic antibacterial, antifungal or antiviral
antibiotics for greater than or equal to 14 days; OR

2. Hospitalization of any duration for infection; OR

3. Isolation of a bacteria, fungus, or virus from biopsy, skin lesion, blood, nasal
washing, bronchoscopy, cerebrospinal fluid or stool likely to be an etiologic agent of
infection.

ii. Chronic pulmonary disease as defined by:

1. Bronchiectasis by x-ray computerized tomography; OR

2. Pulmonary function test (PFT) evidence for restrictive or obstructive disease that is
less than or equal to 60% of predicted for age; OR

3. Pulse oximetry less than or equal to 94% in room air (if patient is too young to
comply with performance of PFTs).

iii. Gastrointestinal enteropathy:

1. Diarrhea-watery stools greater than or equal to 3 times per day (of at least 3 months
duration that is not a result of infection as defined in criterion # i. above); OR

2. Endoscopic evidence (gross and histologic) for enteropathy (endoscopy will only be
performed if medically indicated); OR

3. Other evidence of enteropathy or bacterial overgrowth syndrome, including at least one
of the following: malabsorption of fat soluble vitamin(s), abnormal D-xylose
absorption, abnormal hydrogen breath test, or evidence of protein-losing enteropathy
(for example, increasingly high or frequent dosing of IV gamma globulin supplement
required to maintain blood IgG level).

iv. Poor nutrition: Requires G-tube or IV feeding supplement to maintain weight or
nutrition.

v. Auto- or allo-immunity: Objective physical findings including but are not limited to at
least one of the following: alopecia, severe rashes, uveitis, joint pain with redness or
swelling or limitation of movement that is not a result of infection, lupus-like lesions,
and granulomas (not including auto- or alloimmune enteropathy, which is criterion iii).
Where possible and appropriate, diagnosis will be supported by histopathology or another
diagnostic modality.

vi. Failure to grow in height: less than or equal to 3rd percentile for age.

vii. Skin molluscum contagiosum OR warts (this criterion is satisfied if molluscum consists
of greater than or equal to 10 lesions or there are greater than or equal to 2 lesions at
each of two or more widely separated anatomic sites; or there are greater than or equal to
3 warts at different anatomic sites at the same time; or the patient has both molluscum and
warts).

viii. Mucocutaneous candidiasis (chronic oral thrush or candida esophagitis or candida
intertriginous infection or candida nail infection; must be culture positive to satisfy
this criterion).

ix. Hypogammaglobulinemia: Requires regular IgG supplementation.

- Aged 3-40 years, inclusive.

- Must have a 6/6 HLA-MRD graft available, or an HLA-matched unrelated PBSC graft (10/10
or 9/10 mismatch) available, or a minimum of 4/6 HLA-matched cord blood product
available (if the cord blood graft is less than 5.0x10(7) cells, a second appropriate
4/6 or greater match cord blood product must be available).

- Mismatched MUD and Cord Blood transplants need to have Class I and II HLA antibody
screen, DSA should be avoided.

- Must be HIV negative.

- Must be able to stay within 1 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 (DPA) for health care decisions to an
appropriate adult relative or guardian in accordance to NIH-200 NIH Advance Directive
for Health Care and Medical Research Participation .

- For participants of reproductive potential, must agree to consistently use highly
effective contraception throughout study participation and for at least 3 months after
the study.

Acceptable forms of contraception are:

a. For females:

i. Condoms, male or female, with or without a spermicide;

ii. Diaphragm or cervical cap with spermicide;

iii. Intrauterine device;

iv. Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA-approved
contraceptive method;

v. Male has previously undergone a vasectomy.

b. For males: Condoms or other contraception with partner.

EXCLUSION CRITERIA:

1. Eastern Cooperative Oncology Group (ECOG) or equivalent performance status of 3 or
more (see ECOG performance status guidelines, available at https://ecog-acrin.

org/resources/ecog-performance-status).

2. Left ventricular ejection fraction <40%.

3. Transaminases >5x upper limit of normal based on the patient s clinical situation and
at the discretion of the investigator.

4. Liver alkaline phosphatase >10x upper limit of normal based on the patient s clinical
situation and at the discretion of the investigator.

5. Psychiatric disorder or mental deficiency severe enough as to make compliance with the
BMT treatment unlikely, and/or making informed consent impossible.

6. Major anticipated illness or organ failure incompatible with survival from alloPBSC,
MUD, or unrelated cord blood transplant.

7. Uncontrolled seizure disorder.

8. Any condition that, in the opinion of the investigator, contraindicates participation
in this study.

9. Pregnant or lactating females.

INCLUSION OF VULNERABLE PARTICIPANTS

Children: Children 3 years of age and older may enroll on this study because the condition
under study affects children and the study holds the prospect for direct benefit.

Pregnant and Lactating Women: Pregnant women are excluded from this study due to risks
associated with the study intervention and the effects of the combination of conditioning
medications (h-ATG, busulfan) and total body irradiation on the developing human fetus,
including potential teratogenic or abortifacient effects.

If a study participant or partner of a male subject becomes pregnant or suspects she is
pregnant, the participant should notify the study staff immediately. A female participant
who becomes pregnant will be withdrawn from the study as outlined below. If a female
participant or a partner of a male participant becomes pregnant, the participant will have
contact follow-up with the study team to document the outcome of the pregnancy.

Because there is an unknown but potential risk for AEs in nursing infants secondary to the
mother undergoing the study intervention, breastfeeding should be discontinued if the
mother will undergo the study intervention.

Decisionally Impaired Adults: Adults who are unable to consent are eligible for enrollment
in this protocol because they still benefit clinically from the study. However, the
participant must have a DPA that can give consent. Similarly, enrolled participants who
lose the ability to provide ongoing consent during study participation may continue in the
study. The risks and benefits of participation for adults unable to consent should be
identical to those described for less vulnerable patients.