Title
A Randomized Trial of Low vs. Moderate Exposure Busulfan for Infants with Severe Combined Immunodeficiency (SCID) Receiving TCR alpha beta+/CD19+ Depleted Transplantation: A Phase II study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Transplantation & Cellular Consortium (PTCTC)

Description
Phase II Conditioning SCID Infants Diagnosed Early (CSIDE)

Objective
The purpose of this study is to see if lower doses of a chemotherapy drug called busulfan will help babies with certain types of SCID achieve good immunity after receiving a hematopoietic stem cell transplant (HSCT) that has some immune cells (called T cells) removed

Treatment
Your child will receive either a low or medium dose of the chemotherapy drug busulfan, determined by randomization (selection by chance)

Your child will receive donor stem cells that have been modified to remove most of the T-cell and B-cells

A cheek swab (also called a buccal swab) will be taken from your child prior to the transplant to determine the percentage of donor cells versus your child’s cells in your child’s blood after transplant

Research blood study samples to learn more about SCID and how blood cells help the immune system will be collected before transplant, the day of transplant, and at 7 days, 14 days, 42 days, 100 days, 6 months, 9 months, 1 year, 2 years, and possibly 3 years post-transplant

Approximately 9-18 months after transplant, vaccinations will be administered, and a blood test measuring whether your child’s body has responded to the vaccine will be collected

Key Eligibility
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 less than 300/microliter AND no or very low T cell function (less than 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): less than 50% of lower limit of normal T cell function as measured by response to PHA OR < less than 30% of lower limit of normal T cell function as measured by response to CD3 Absent or less than 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 less than 1500/microliter, ii. greater than 80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR less than 80% of CD3+ or CD4+ T cells are CD62L negative AND/OR greater than 50% of CD3+ or CD4+ T cells express HLA-DR (at less than 4 years of age) AND/OR are oligoclonal T iii. Low TRECs and/or the percentage of D4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower level of normal

Omenn syndrome: as defined by the protocol

Documented mutation in one of the following SCID-related genes: as defined by the protocol

No available genotypically matched related donor (sibling)

Availability of a suitable donor and graft source as defined by the protocol

Age 0 to 2 years at enrollment

Adequate organ function as defined by the protocol

EXCLUSION

Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen as defined by the protocol

Patients with HIV or HTLV I/II infection will be excluded

Applicable Disease Sites
Hematologic cancers, other; Unknown Sites

Participating Institutions
UW Health University Hospital