Stem Cell Transplantation for Sickle Cell Anemia
Palabras clave
Abstracto
Descripción
Primary objective:
1) To determine disease free survival (DFS) at one year after matched sibling transplant using either bone marrow (BM), peripheral blood stem cells (PBSC), or umbilical cord blood (UCB) after a conditioning regimen consisting of Alemtuzumab, Fludarabine, and Melphalan in patients 2-30 y/o
Secondary objectives:
1. Overall survival
2. Rate of neutrophil and platelet engraftment for BM vs. UCB
3. Incidence of graft failure
4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
5. Incidence of chronic GVHD
6. Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
8. Incidence of invasive fungal disease
9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels
fechas
| Verificado por última vez: | 06/30/2020 |
| Primero enviado: | 06/11/2013 |
| Inscripción estimada enviada: | 06/12/2013 |
| Publicado por primera vez: | 06/13/2013 |
| Última actualización enviada: | 07/13/2020 |
| Última actualización publicada: | 07/15/2020 |
| Fecha de inicio real del estudio: | 05/31/2011 |
| Fecha estimada de finalización primaria: | 08/31/2020 |
| Fecha estimada de finalización del estudio: | 08/31/2020 |
Condición o enfermedad
Intervención / tratamiento
Drug: Related donor
Drug: Related donor
Drug: Related donor
Procedure: Related donor
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| Experimental: Related donor Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
-22 Alemtuzumab 3mg IV (test dose)
-21 Alemtuzumab 10mg IV
-20 Alemtuzumab 15mg IV
-19 Alemtuzumab 20mg IV
-8 Fludarabine 30mg/m2 IV
-7 Fludarabine 30mg/m2 IV
-6 Fludarabine 30mg/m2 IV
-5 Fludarabine 30mg/m2 IV
-4 Fludarabine 30mg/m2 IV
-3 Melphalan 140mg/m2 IV
-2 Rest Day
-1 Rest Day
0 Stem Cell Infusion | Drug: Related donor Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]
b) Medications
i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below |
Criterio de elegibilidad
| Edades elegibles para estudiar | 2 Years A 2 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | Inclusion Criteria: - Patient Eligibility 1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight) 1. Age 2-30 2. Hb SS, S-thal0, S-thal+, SC 3. Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2 4. Karnofsky/Lansky score >50 5. LVSF>26% or LVEF>40% 6. DLCO >40% or O2 sat >85% for those patients that can't perform PFTs 7. GFR >70 and serum creatinine < 1.5 * ULN for age 8. ALT and AST < 5 x ULN, direct bilirubin <2 x ULN 9. If the patient has been on chronic transfusion or has a ferritin >1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis - Exclusion criteria 1. Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen 2. Pregnant or breastfeeding 3. HIV positive 4. Written informed consent not obtained |
Salir
Medidas de resultado primarias
1. Graft Failure [1 year]
Medidas de resultado secundarias
1. Overall survival [2 years]
