Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- Drug: Alemtuzumab, low dose total body irradiation, Sirolimus
- Registration Number
- NCT03587272
- Lead Sponsor
- Robert Nickel
- Brief Summary
This multisite prospective study seeks to determine if HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, "SUN") can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).
- Detailed Description
This is a prospective, multicenter phase II study of HLA-identical sibling donor HSCT in 30 pediatric patients with SCD using nonmyeloablative conditioning with alemtuzumab, total-body irradiation, and sirolimus. The primary Objective of this study is to determine if the SUN regimen can decrease the incidence of grade II-IV acute graft-versus host disease (GVHD) by day +100 while maintaining similar disease-free survival compared to establish HLA-identical donor hematopoietic stem cell transplant (HSCT) regimens in children with SCD. The secondary Objective is to determine if health-related quality of life (HRQoL) for children undergoing SUN HSCT is preserved during the early post-transplant time period. To determine if the SUN regimen can decrease the number of platelet transfusions compared to established HLA-identical HSCT regimens in children with SCD. The tertiary/Exploratory Objectives: To describe other markers of toxicity (duration of neutropenia, mucositis, length of hospitalization) and indicators of a successful HSCT (HRQoL at 1 year, proportion needing additional immunosuppression during the first year, proportion able to wean sirolimus at 1 year).
With protocol version 5.0, added new secondary objective to determine if the change from intravenous to subcutaneous alemtuzumab and the addition of post-HSCT G-CSF can decrease the incidence of poor donor engraftment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
Not provided
- General: Life expectancy less than 6 months. Pregnant or breastfeeding patients.
- Infection Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active Hepatitis B or C determined by serology and/or NAAT are excluded.
- Liver: Direct (conjugated) bilirubin > 1.5 mg/dL, transaminases >5x upper limit of normal for age.
- Cardiac: Left ventricular shortening fraction <25% or ejection fraction <50% by ECHO.
- Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2.
- Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin). Baseline oxygen saturation <85% or PaO2 <70.
- Heme: History of RBC alloantibodies against donor RBC antigens (even if current antibody screen is negative). Major ABO incompatibility with donor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SUN regimen Alemtuzumab, low dose total body irradiation, Sirolimus Alemtuzumab, low dose total body irradiation, Sirolimus HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, "SUN") can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).
- Primary Outcome Measures
Name Time Method Acute GVHD 100 days post transplant Acute grade II-IV GVHD
- Secondary Outcome Measures
Name Time Method PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory Day +30, and day +100 post transplant PedsQL 4.0 assessments of health related quality of life before/after transplant
Poor donor engraftment day +365 graft rejection, stem cell boost, or 1-year donor myeloid chimerism \<50%
Trial Locations
- Locations (7)
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Columbia University
🇺🇸New York, New York, United States
Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada