Sirolimus Prophylaxis for aGVHD in TME SCID

Study Overview
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Brief Summary
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Study Design: SCID infants receiving an unconditioned haploidentical transplant will be started on Sirolimus (0.05 mg/kg/day) day -5 for Acute Graft-Versus-Host Disease (aGVHD) prophylaxis. Sirolimus levels will be monitored with goal sirolimus trough level of 5-8 ng/mL. Patients will be monitored for signs of aGVHD as defined by UCSF SOP CL 221.06 through day +100. Sirolimus will be tapered once T-regulatory cell to CD4 effector cell ratio is > or = 9%. Setting: Inpatient BMT Unit Benioff Children's Hospital at UCSF Medical Center Study Subjects: 15 infants with diagnosis of maternally engrafted T cells SCID by CA Newborn screen receiving unconditioned haploidentical HSCT Main Outcome Measures: Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by SOP CL 221.06 by Day +100. Hypothesis 1. Patients placed on sirolimus prophylaxis will have lower incidence of aGVHD compared to historical controls. Hypothesis 2. Lower doses of sirolimus milligram per kilogram will be required to maintain goal troughs of 5-8 ng/mL.

Official Title
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Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT)

Conditions
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Severe Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell Transplant

Intervention / Treatment
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* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants diagnosed with SCID on CA newborn screen Evidence of Maternal Engraftment Unconditioned haploidentical hematopoeitic stem cell transplant Exclusion Criteria: Evidence of acute graft vs. host disease

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sirolimus<br>Sirolimus (0.05 mg/kg/day) day -5 for aGVHD prophylaxis through day +100 or until T-regulatory cells >9% of CD4 effector cells; whichever comes first. | Drug: Sirolimus<br> <br> * Other names: Rapamune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of aGVHD | Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by UCSF SOP CL 221.06 by Day +100. | 105 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-regulatory cell enumeration | T-regulatory cell enumeration studies by blood draw prior to prophylaxis and at day +30, day+60, day+100. | 105 days | 
| Sirolimus therapeutic drug monitoring | Sirolimus therapeutic drug monitoring will be done via blood draws(after initial 4th dose; thereafter every 4th dose with adjustment; once stable it will be measured weekly). We will determine the average dose in milligrams per kilograms that would be needed to reach therapeutic trough levels of 5-8 ng/mL. | 105 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCID, severe combined immunodeficiency, maternal engraftment, aGVHD prophylaxis, sirolimus