NCT04370795

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

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 3 Years – 40 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is an open-label pilot study of human leukocyte antigen (HLA)-matched related and unrelated donor hematopoietic stem cell (HSC) transplant (also referred to as peripheral blood stem cell \[PBSC\] transplant or bone marrow transplant \[BMT\]) for up to 20 patients with severe combined immune deficiency (SCID). SCID is most commonly caused by mutations in the IL2RG gene encoding the interleukin (IL) receptor signaling gamma chain (gamma c); however, patients with JAK-3 mutations have the same phenotypes and are similarly affected. The study population is older children (greater than or equal to 3 years of age) and adults (less than or equal to 40 years of age) who are experiencing deteriorating and/or dysfunctional immunity and/or any of a constellation of severe or chronic medical problems warranting transplantation. The study is designed to evaluate whether the use of uniquely designed transplant conditioning either containing total body irradiation (TBI) or not, along with a graft-versus-host disease (GvHD) prevention regimen achieves sufficient engraftment of donor HSCs to facilitate robust restoration of cellular immunity (T cell/natural killer \[NK\] cell number and function) including thymic function, and humoral immunity (B cell number and function), while at the same time enhancing tolerance of the donor graft in a fashion that reduces the occurrence of GvHD but not significantly enhancing the risk of post-transplant viral infection. One target population is SCID patients who received matched sibling or haploidentical lymphocyte-depleted transplants as infants with little or no myeloid conditioning, resulting in variable restoration of T cell immunity, but little or no restoration of NK or B cell immunity. Another target population is SCID patients with partial production or function of gamma c or JAK3 or SCID patients with clonal somatic reversion of the mutation in the IL2RG or JAK-3 gene, who have less severe immune deficiency in childhood. A subset of patients from all of these target SCID populations may experience progressive deterioration of immune function leading to acute and chronic medical problems that warrant consideration of allogeneic transplant to restore immunity. The conditioning and GvHD prevention regimens for this HSC transplant protocol are designed to use mobilized PBSCs or bone marrow (if mobilization is not possible) from either an HLA-matched related donor (MRD) as first choice or from an HLA-matched unrelated donor (MUD) for those without an appropriate HLA-MRD. If there is no appropriate MRD nor MUD adult donor available, then an appropriate cord blood from the cord blood registries may be used for small children SCID recipients. We propose using a busulfan-based, nonmyeloablative conditioning regimen plus or minus TBI combined with horse anti-thymocyte globulin (h-ATG) immune suppression conditioning plus post-transplant sirolimus as a tolerance-inducing immunosuppressant to prevent GvHD.

Conditions

• Severe Combined Immune Deficiency (SCID)

Interventions

Type	Name	Description
DRUG	Sirolimus	Post transplant immunosuppressant drug
DRUG	Busulfan	Conditioning drug
DRUG	Horse -Anti-thymocyte	Immune suppression conditioning drug
DRUG	G-CSF	Used to prevent infection and neutropenic fevers caused by chemotherapy
RADIATION	Total Body Irradiation (TBI)	Conditioning (only patients in Group 1 will receive TBI)

Timeline

• Start date: 2025-11-26
• Primary completion: 2025-11-26
• Completion: 2025-11-26
• First posted: 2020-05-01
• Last updated: 2025-12-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study