RECRUITING

Conditioning SCID Infants Diagnosed Early

Description

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.

Conditions

SCID
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Related Conditions:

SCID

Study Overview

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Study Details

Study overview

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.

A Randomized Trial of Low Versus Moderate Exposure Busulfan for Infants With Severe Combined Immunodeficiency (SCID) Receiving TCRαβ+/CD19+ Depleted Transplantation: A Phase II Study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Blood and Marrow Transplant Consortium (PBMTC)

Conditioning SCID Infants Diagnosed Early

Condition
SCID
Intervention / Treatment

-

Contacts and Locations

Birmingham

Univeristy of Alabama at Birmingham, Birmingham, Alabama, United States, 35294

Phoenix

Mayo Clinic Arizona and Phoenix Children's Hospital, Phoenix, Arizona, United States, 85016

Los Angeles

Children's Hospital Los Angeles, Los Angeles, California, United States, 90027

Los Angeles

UCLA Center for Health Sciences, Los Angeles, California, United States, 90095

San Diego

Rady Children's Hospital, San Diego, San Diego, California, United States, 92123

San Francisco

University of California San Francisco Medical Center - Peds, San Francisco, California, United States, 94143

Stanford

Lucile Packard Children's Hospital / Stanford Children's Health, Stanford, California, United States, 94305

Aurora

University of Colorado - Children's Hospital, Aurora, Colorado, United States, 80045

Wilmington

Nemours Alfred I. duPont Hospital for Children, Wilmington, Delaware, United States, 19803

Washington

Children's National Medical Center, Washington, District of Columbia, United States, 20010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Infants with SCID, either typical or leaky or Omenn syndrome.
  • 1. 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
  • 2. Leaky SCID is defined as the following
  • 3. 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.
  • 1. Hepatomegaly
  • 2. Splenomegaly
  • 3. Lymphadenopathy
  • 4. Elevated IgE
  • 5. Elevated absolute eosinophil count
  • 6. \*Oligoclonal T cells measured by CDR3 length or flow cytometry (upload report)
  • 7. \*Proliferation to PHA is reduced to \< 50% of lower limit of normal (LLN) or SI \< 30
  • 8. \*Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells below the lower level of normal
  • 2. Documented mutation in one of the following SCID-related genes
  • 1. Haploidentical related mobilized peripheral blood cells
  • 2. 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
  • 6. Adequate organ function defined as:
  • 1. Cardiac:
  • 2. Hepatic:
  • 3. Renal:
  • 4. Pulmonary No need for supplemental oxygen and O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care).
  • 1. 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:
  • 2. Patients with HIV or HTLV I/II infection will be excluded.

Ages Eligible for Study

0 Years to 2 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Michael Pulsipher, MD,

Sung-Yun Pai, MD, STUDY_CHAIR, National Institutes of Health (NIH)

Michael Pulsipher, MD, STUDY_CHAIR, Children's Hospital Los Angeles

Study Record Dates

2026-08-01