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Lower dose chemotherapy for infants with SCID

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)

Phase 2 Interventional Center for International Blood and Marrow Transplant Research · NCT03619551

This study is testing if giving lower doses of chemotherapy to infants with Severe Combined Immunodeficiency (SCID) can help them recover their immune system better and with fewer side effects after a stem cell transplant.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment56 (estimated)
Ages0 Years to 2 Years
SexAll
SponsorCenter for International Blood and Marrow Transplant Research Research network
Drugs / interventionschemotherapy, fludarabine
Locations52 sites (Birmingham, Alabama and 51 other locations)
Trial IDNCT03619551 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of lower doses of busulfan chemotherapy in infants diagnosed with Severe Combined Immunodeficiency (SCID). The study aims to determine if these reduced doses can help achieve better immune recovery with fewer complications after stem cell transplantation. Infants will be enrolled based on their specific SCID subtype and will receive transplants from unrelated or haploidentical donors. The trial will monitor immune recovery by assessing T and B cell responses to immunizations post-transplant.

Who should consider this trial

Good fit: Ideal candidates for this study are infants diagnosed with SCID, including typical, leaky, or Omenn syndrome.

Not a fit: Patients with SCID who do not meet the specific inclusion criteria or those with severe infections at the time of enrollment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved immune function in SCID infants with reduced risks of complications.

How similar studies have performed: Other studies have shown promise with reduced chemotherapy approaches in similar patient populations, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion 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

   • 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.
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

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

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

Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:

For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks

6. Adequate organ function defined as:

1. Cardiac:

   Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥ 26% by echocardiogram.
2. Hepatic:

   Total bilirubin \< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and ALT \< 5.0 x ULN for age.
3. Renal:

   GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m2.
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).

Exclusion Criteria:

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:

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

Where this trial is running

Birmingham, Alabama and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions SCID
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.