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

NCT04370795 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 20003720-I-0037
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Severe Combined Immune Deficiency (SCID)

Keywords

Post-Transplant; Hematopoietic; Allogeneic; Graft-Versus-Host Disease; Irradiation

Outcome Measures

Primary Outcomes (2)

• Engraftment rate of > 80%

  Engraftment rate of greater than or equal to 80% of patients achieving greater than or equal to 50% stable myeloid chimerism with or without the use of TBI.

  six months and one year

• Engraftment with no grade 3 GvHD

  Engraftment as such should not occur with any Grade 3 or higher acute GvHD at Day 100 nor occurrence of extensive chronic GvHD

  Day 100 and one year

Secondary Outcomes (2)

• Donor B cell engraftment

  one year post transplant

• Donor T cell engraftment

  one year post transplant

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Patients will be treated with Total Body Irradiation (TBI)

Drug: Sirolimus; Drug: Busulfan; Drug: Horse -Anti-thymocyte; Drug: G-CSF; Radiation: Total Body Irradiation (TBI)

Group 2

ACTIVE COMPARATOR

Patients will not be treated with Total Body Irradiation (TBI)

Drug: Sirolimus; Drug: Busulfan; Drug: Horse -Anti-thymocyte; Drug: G-CSF

Interventions

Sirolimus DRUG

Post transplant immunosuppressant drug

Group 1; Group 2

Busulfan DRUG

Conditioning drug

Group 1; Group 2

Horse -Anti-thymocyte DRUG

Immune suppression conditioning drug

Group 1; Group 2

G-CSF DRUG

Used to prevent infection and neutropenic fevers caused by chemotherapy

Group 1; Group 2

Total Body Irradiation (TBI) RADIATION

Conditioning (only patients in Group 1 will receive TBI)

Group 1

Eligibility Criteria

• Age: 3 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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):
• Treatment (not prophylaxis) with systemic antibacterial, antifungal or antiviral antibiotics for greater than or equal to 14 days; OR
• Hospitalization of any duration for infection; OR
• 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:
• Bronchiectasis by x-ray computerized tomography; OR
• Pulmonary function test (PFT) evidence for restrictive or obstructive disease that is less than or equal to 60% of predicted for age; OR
• 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:
• 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
• Endoscopic evidence (gross and histologic) for enteropathy (endoscopy will only be performed if medically indicated); OR
• 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).

You may not qualify if:

• 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).
• Left ventricular ejection fraction \<40%.
• Transaminases \>5x upper limit of normal based on the patient s clinical situation and at the discretion of the investigator.
• Liver alkaline phosphatase \>10x upper limit of normal based on the patient s clinical situation and at the discretion of the investigator.
• Psychiatric disorder or mental deficiency severe enough as to make compliance with the BMT treatment unlikely, and/or making informed consent impossible.
• Major anticipated illness or organ failure incompatible with survival from alloPBSC, MUD, or unrelated cord blood transplant.
• Uncontrolled seizure disorder.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.
• Pregnant or lactating females.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Graft vs Host Disease

Interventions

Sirolimus; Busulfan; Granulocyte Colony-Stimulating Factor; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Elizabeth M Kang, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 1, 2020
• Study Start: November 26, 2025
• Primary Completion: November 26, 2025
• Study Completion: November 26, 2025
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

US (1)