Clinical Research Directory

Studies of the Pathogenesis of HIV Infection in Human Peripheral Blood Cells and/or Body Fluids in People Living With and Without HIV

We are studying virologic and/or immunologic parameters of HIV infection and other infectious or non-infectious immune deficiency diseases in order to better understand the pathogenesis of HIV. Because of the lack of an adequate animal model it is generally necessary to utilize human peripheral blood cells for studying aspects of either in vivo or in vitro HIV infection. We wish to be able to continue to elucidate many pathogenic aspects of HIV infection in relation to other infectious or non-infectious immune regulation and dysregulation using human peripheral blood mononuclear cells as a model.

Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders

This Phase II pilot study evaluates the safety and effectiveness of reduced-intensity conditioning (RIC) regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients with non-malignant disorders, including immunodeficiencies and hemoglobinopathies. The study examines different conditioning approaches that vary in the timing and dosing of alemtuzumab (Campath), as well as disease-specific modifications for beta thalassemia major and infants. The primary objective is to assess donor engraftment and event-free survival at one year following transplant. The study aims to determine whether RIC regimens can reduce toxicity while maintaining successful engraftment and disease control.

Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)

This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) in patients with non-malignant or malignant diseases. This regimen, consisting of busulfan, fludarabine, and low dose total body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve an acceptable level of donor-derived engraftment following a previous allogeneic HCT.

Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC

The goal of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia IRB approved protocols that utilize CliniMACs technology for T depletion.

V-IMMUNE: A Novel Immunoglobulin Therapy for Immunodeficiency

This is a phase III, non-randomized clinical trial (VIP Study) designed to assess the safety and efficacy of V-IMMUNE®, a 5% human normal immunoglobulin preparation, in approximately 50 patients with primary immunodeficiency (PID). Participants, all aged ≥2 years and already receiving IVIG therapy, will be switched to V-IMMUNE® at a dose of 600 mg/kg every three weeks via intravenous infusion. The study will use historical data as a control and extend over 12 months, with scheduled visits at each infusion (an estimated 17 infusions per participant). Objectives and Outcomes Primary Efficacy Endpoint: Rate of serious bacterial infections over 12 months. Primary Safety Endpoint: Proportion of infusions with one or more temporally associated adverse events (AEs). Secondary Endpoints: Additional safety outcomes (e.g., average number of AEs within 72 hours per infusion), efficacy measures (non-serious bacterial infections, time to resolution, antibiotic use, hospitalizations), and quality of life (SF-36) at 6 and 12 months. A pharmacokinetic (PK) sub-study will be conducted in 20 participants aged ≥16 years to evaluate total IgG levels, half-life, AUC, Cmax, and other PK parameters. Study Design and Intervention V-IMMUNE® is given at an initial infusion rate of 0.01 mL/kg/min for 30 minutes, increasing stepwise up to 0.06 mL/kg/min if well tolerated. Pre-medication, including rapid IV saline, diphenhydramine, and hydrocortisone, will be administered for the first three months to reduce the risk of infusion-related AEs. Patients at elevated thromboembolic risk will receive the lowest feasible infusion rate. Sample Size and Analysis Fifty patients total will be enrolled to ensure adequate power to demonstrate a severe infection rate below one event per person-year (with a one-sided 1% significance level). Safety endpoints will be met if the upper bound of the 95% confidence interval for the proportion of temporally associated infusion-related AEs remains below 40%, assuming a true rate under 20%. An interim analysis is planned at six months or upon reaching 50% enrollment. 20 patients at total including adults and \<16 years old, 6 children from 2 to 12 years old and 6 children from 12 to 16 years old.

Alpha/Beta T and CD19+ Depleted Peripheral Stem Cells for Patients With Primary Immunodeficiencies

This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell grafts from unrelated or partially matched related donors. There are two conditioning regimens depending upon patient diagnosis and age.