Conditioning SCID Infants Diagnosed Early

Running, not enrolling · Phase 2

Conditions studied: SCID

In brief

The investigators want to study if lower doses of chemotherapy will help babies with SCID to achieve good immunity with less short and long-term risks of complications after transplantation. This trial identifies babies with types of immune deficiencies that are most likely to succeed with this approach and offers them transplant early in life before they get severe infections or later if their infections are under control. It includes only patients receiving unrelated or mismatched related donor transplants. The study will test if patients receiving transplant using either a low dose busulfan or a medium dose busulfan will have immune recovery of both T and B cells, measured by the ability to respond to immunizations after transplant. The exact regimen depends on the subtype of SCID the patient has. Donors used for transplant must be unrelated or half-matched related (haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T cells removed, using a newer, experimental approach of a well-established technology. Once the stem cell transplant is completed, patients will be followed for 3 years. Approximately 9-18 months after the transplant, vaccinations will be administered, and a blood test measuring whether your child's body has responded to the vaccine will be collected.

Key facts

Study ID

NCT03619551

Run by

Center for International Blood and Marrow Transplant Research

People needed

56

Starts

2018-10-22

Expected to finish

2028-12-01

Last updated by the study team

2026-08-06

Who can join

Age: any, up to 2. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Infants with SCID, either typical or leaky or Omenn syndrome.
• Typical SCID is defined as either of the following
• Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin OR
• Presence of maternally derived T cells
• Leaky SCID is defined as the following
• Absence of maternally derived T cells
• AND either one or both of the following (i, ii): i) <50% of lower limit of normal T cell function as measured by response to PHA OR <30% of lower limit of normal T cell function as measured by response to CD3 ii) Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (must document post vaccination or exposure for this criterion to apply)
• AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
• Omenn syndrome • Generalized skin rash
• Maternal lymphocytes tested for and not detected.
• >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of age)
• Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to antigens (Candida, tetanus) to which the patient has been exposed IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible as Omenn Syndrome.
• Hepatomegaly
• Splenomegaly
• Lymphadenopathy
• Elevated IgE
• Elevated absolute eosinophil count
• *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload report)
• *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or SI < 30
• *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells below the lower level of normal
• Documented mutation in one of the following SCID-related genes
• a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1, RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a suitable donor and graft source
• Haploidentical related mobilized peripheral blood cells
• 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment
• Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:

You may not qualify if…

• Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen. Serious infections as defined below that occur after enrollment must be reported immediately to the Study Coordinating Center, and enrollment will be put on hold until the infection resolves. Ideally enrolled subjects will not have had any infection. If patients have experienced infections, these must have resolved by the following definitions:
• a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site must be negative and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
• ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
• iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). If possible, radiographic resolution should also be demonstrated.
• b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site is negative and patient has completed appropriate course of antifungal therapy (typically at least 14 days). The patient may be continued on antifungal prophylaxis following completion of the treatment course.
• c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of therapy (typically at least 21 days). If possible, radiographic resolution should also be demonstrated. The patient may be continued on prophylaxis following completion of the treatment course.
• d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must be re-tested and are negative.
• ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible, radiographic resolution should also be demonstrated.
• Patients with HIV or HTLV I/II infection will be excluded.

Where it is running

• Univeristy of Alabama at Birmingham — Birmingham, Alabama, United States
• Mayo Clinic Arizona and Phoenix Children's Hospital — Phoenix, Arizona, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• UCLA Center for Health Sciences — Los Angeles, California, United States
• Rady Children's Hospital, San Diego — San Diego, California, United States
• University of California San Francisco Medical Center - Peds — San Francisco, California, United States
• University of Colorado - Children's Hospital — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Shands HealthCare & University of Florida — Gainesville, Florida, United States
• University of Miami/Jackson Memorial Hospital — Miami, Florida, United States
• All Children's Hospital — St. Petersburg, Florida, United States
• Children's Healthcare of Atlanta at Egleston — Atlanta, Georgia, United States
• Comer Children's Hospital/University of Chicago Medicine — Chicago, Illinois, United States
• Indiana University Hospital/Riley Hospital for Children — Indianapolis, Indiana, United States
• University of Iowa Hospitals & Clinics — Iowa City, Iowa, United States
• Children's Hospital / LSUHSC — New Orleans, Louisiana, United States
• Dana Farber Cancer Institute - Peds — Boston, Massachusetts, United States
• The University of Michigan — Ann Arbor, Michigan, United States
• Helen DeVos Children's — Grand Rapids, Michigan, United States
• University of Minnesota Blood and Marrow Transplant Program - Pediatrics — Minneapolis, Minnesota, United States
• The Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
• Nebraska Medicine — Omaha, Nebraska, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Morgan Stanley Children's Hospital of New York-Presbyterian - Columbia University Medical Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center - Peds — New York, New York, United States

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