Sirolimus Prophylaxis for aGVHD in TME SCID

Phase 2

Withdrawn

• Conditions: Stem Cell Transplant; Severe Combined Immunodeficiency; Transplacental Maternal Engraftment
• Interventions: Drug: Sirolimus

• Registration Number: NCT02177760
• Lead Sponsor: University of California, San Francisco

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-19
• Study First Submitted QC: 2014-06-27
• Study First Posted: 2014-06-30
• Study Start: 2014-07
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-01
• Last Update Posted: 2015-12-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sirolimus	Sirolimus	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.

Primary Outcome Measures

Name	Time	Method
Incidence of aGVHD	105 days	Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by UCSF SOP CL 221.06 by Day +100.

Secondary Outcome Measures

Name	Time	Method
Sirolimus therapeutic drug monitoring	105 days	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.
T-regulatory cell enumeration	105 days	T-regulatory cell enumeration studies by blood draw prior to prophylaxis and at day +30, day+60, day+100.

Trial Locations

Locations (1)

Benioff Children's Hospital at UCSF Medical Center; 🇺🇸 San Francisco, California, United States