Haplo-identical Hematopoietic Stem Cell Transplantation Following Reduced-intensity Conditioning in Children With Neuroblastoma
Summary
To date, no curative option exists for patients with relapsed or refractory stage IV neuroblastoma after previous autologous stem cell transplantation. Our preliminary results of RIC allo-HSCT (protocol RICE) indicate the feasability and low toxicity of allograft in heavily pre-treated children. Furthermore RIC SCT and immunomagnetic CD3/CD19 graft depletion may allow HHCT with lower toxicity and faster engraftment. CD3/CD19 depleted grafts not only contain CD34+ stem cells but also graft-facilitating cells, CD34- progenitors, dendritic and natural killer cells which may allow stable engraftment and participate to GvT effect.
After haploidentical stem cell transplantation anti tumour activity exerted by donor derived NK cells could be stimulated by NK cells injections. Those effects may help to reduce the relapse rate and to impove the outcome of those patients. The investigators prospectively evaluated engraftment and immune reconstitution.
Description
This RICE NK protocol is a multicenter study of Haplo- HSCT using RIC with fludarabine (180 mg/m2), Busulfan IV (3,2 to 4,8 mg/kg/d), TBI 2 grays and CD3/CD19 graft depletion. A minimum of 8 106 CD34+ cells/kg were infused on day 0. No post grafting immunosuppression was applied if the graft contained < 2.5 x 104 CD3+ cells/kg. At Day 30 and 60 post-graft we perform an donor CD56+ cells injection. The investigators develop this strategy in an European collaboration working on haploidentical stem cell transplantation for childhood refractory and metastatic solid tumors.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Neuroblastoma
Intervention
Busulfan - Fludarabine - TBI
Location
CHU Clermont-Ferrand
Clermont-Ferrand
France
63003
Status
Not yet recruiting
Source
University Hospital, Clermont-Ferrand
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01156350
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:12:25-0400
Clinical Trials
Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support
Objectives: 1. To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludar...
Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide
The goal of this clinical research study is to learn if cyclophosphamide given after busulfan and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which tra...
The purpose of this study is to evaluate the OS, RFS, and TRM after HCT with low-dose total body irradiation, fludarabine, and busulfan conditioning.
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before a donor stem cell transplant helps stop the growth of tumor cells. It may a...
Double Cord Blood Transplantation
Double umbilical cord blood transplantation (DUCBT) following high dose or reduced intensity conditioning will be well-tolerated and result in a high degree of engraftment in patients with...
PubMed Articles
High-risk neuroblastoma is characterized by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). The benefits of a tandem high-d...
Busulfan is commonly used as a conditioning regimen before hematological stem cell transplantation (HSCT). There is a big inter-individual variability in busulfan exposure and the narrow therapeutic i...
Busulfan is commonly used for cancer chemotherapy. Although it has the advantage of increasing the survival rate of patients, it can cause male infertility via damaging the testes and reducing sperm c...
RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children.
Two new neuroblastoma susceptibility loci at 3q25 (RSRC1 rs6441201 G > A) and 4p16 (CPZ rs3796725 T > C and rs3796727 A > G) were identified by a genome-wide association study (GWAS) invol...
We successfully used a haploidentical transplantation protocol with posttransplant cyclophosphamide (CY) (50 mg/kg/d on days +3 and +4) for in vivo T-cell depletion in patients with mucopolysacchari...
Medical and Biotech [MESH] Definitions
Busulfan
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
Staurosporine
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Esthesioneuroblastoma, Olfactory
A malignant olfactory neuroblastoma arising from the olfactory epithelium of the superior nasal cavity and cribriform plate. It is uncommon (3% of nasal tumors) and rarely is associated with the production of excess hormones (e.g., SIADH, Cushing Syndrome). It has a high propensity for multiple local recurrences and bony metastases. (From Holland et al., Cancer Medicine, 3rd ed, p1245; J Laryngol Otol 1998 Jul;112(7):628-33)
Ganglioneuroblastoma
A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with HORNER SYNDROME and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea.
Genes, Intracisternal A-particle
Genes of IAP elements (a family of retrovirus-like genetic elements) which code for virus-like particles (IAPs) found regularly in rodent early embryos. ("Intracisternal" refers to the cisternae of the endoplasmic reticulum.) Under certain circumstances, such as DNA hypomethylation they are transcribed. Their transcripts are found in a variety of neoplasms, including plasmacytomas, neuroblastoma, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas.
