Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory High-Risk NBL.
|ClinicalTrials.gov Identifier: NCT00874315|
Recruitment Status : Withdrawn (lack of accrual)
First Posted : April 2, 2009
Last Update Posted : October 16, 2015
RATIONALE: - Relapsed or refractory Neuroblastoma (NBL) carries a very poor prognosis and children with relapsed NBL have an overall 3 year survival rate of < 10%. Hematopoietic Stem Cell Transplant from a different donor (allogeneic), is a form of adoptive cellular therapy , such that infused donor cells find host tumors as foreign and fight them. After transplant, the donor immune cells (i.e. T cells, NK cells) mediate Graft versus Tumor (GVT) effect and may stop tumor from recurring. Also,reduced intensity transplants lead to minimal toxicity and less risk of mortality in heavily pre-treated NBL patients.
PURPOSE: This phase II trial is studying how well giving a reduced intensity(using Fludarabine, Busulfan and antithymocyte globulin)preparative regimen followed by donor stem cell transplant works in treating young patients with high-risk neuroblastoma that has relapsed or not responded to treatment.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Other: anti-thymocyte globulin Drug: busulfan Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation||Phase 2|
- To determine the feasibility of allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning regimen comprising fludarabine phosphate, busulfan, and anti-thymocyte globulin, in terms of donor engraftment, transplant-related mortality, and development of acute and chronic graft-vs-host disease, in pediatric patients with high-risk relapsed or refractory neuroblastoma.
- To elucidate the role of natural killer (NK) cells as effectors of graft-vs-tumor effect in these patients.
- To evaluate the role of killer immunoglobulin-like receptor (KIR) mismatches in the donor-recipient pairs on the outcomes of these patients.
- To determine the incidence of progression-free survival at 1 year post-transplantation in these patients.
OUTLINE: This is a multicenter study.
- Reduced-intensity conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour on days -10 to -6, busulfan IV over 2 hours once on day -10 (test dose) and then every 6 hours on days -5 and -4, and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1 and on day 2.
- Transplantation: Patients undergo allogeneic bone marrow or G-CSF-mobilized peripheral blood stem cell transplantation on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine or tacrolimus IV or orally beginning on day -2 and continuing until day 60 or day 100, followed by a taper until day 100 or day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally on days 1-30, followed by a taper until day 60 in the absence of GVHD.
Blood samples are collected at baseline and on days 30, 60, and 100 for correlative laboratory studies. Samples are analyzed for killer immunoglobulin-like receptor (KIR) mismatches by genotyping and immunophenotyping methods (PCR and flow cytometry); natural killer (NK) cell reconstitution by flow cytometry; and NK cell function, NK cell allo-reactivity by ELISPOT and ELISA.
After completion of study treatment, patients are followed periodically for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Pilot Study of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation With In-vivo T-cell Depletion to Evaluate the Role of NK Cells and KIR Mis-matches in Relapsed or Refractory High-risk Neuroblastoma.|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||June 2012|
- Other: anti-thymocyte globulin
2.5 mg/kg/day for 4 doses on day -3, -2 , -1 and day +2.Other Name: Thymoglobulin
- Drug: busulfan
0.8 mg/kg/dose for total of 8 doses.Other Name: Busulfex
- Drug: cyclosporine
1.5 mg/kg/dose every 12 hours.Other Name: Sandimmune, Gengraf, Neoral.
- Drug: fludarabine phosphate
30 mg/m2/day for 5 days.Other Name: Fludara
- Drug: mycophenolate mofetil
15 mg/kg/dose every 8 hoursOther Name: Cell-cept
- Drug: tacrolimus
0.03 mg/kg/day as continuous infusion or 12 hour divided doses
- Procedure: allogeneic hematopoietic stem cell transplantation
Donor stem cell transplantation from HLA matched sibling donor or an unrelated donor.
- Feasibility as measured by the incidence of donor engraftment, transplant-related mortality, and grade III-IV acute graft-vs-host disease (GVHD) at day 100 and the incidence of extensive chronic GVHD within the first year post-transplantation [ Time Frame: 100 days post-HSCT ]The safety and feasibility of reduced intensity allogeneic HSCT will be established in this population by monitoring the incidence of adverse events- 100 day mortality,incidence of severe acute GVHD and non-engraftment of donor cells.
- Progression-free survival (PFS) at 1 year [ Time Frame: 1 year post- HSCT ]
- Relationship between biologic endpoints (e.g., number of natural killer [NK] cells infused, NK cell recovery, and NK cell chimerism status) and clinical endpoints (e.g., donor engraftment, acute GVHD, transplant-related mortality, and PFS) [ Time Frame: 3 and 6 months post-SCT ]
- Relationship between presence of killer immunoglobulin-like receptor (KIR) mismatches and clinical endpoints [ Time Frame: 3 and 6 months post-HSCT ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00874315
|United States, Illinois|
|Children's Memorial Hospital|
|Chicago, Illinois, United States|
|United States, New York|
|Morgan Stanley Children's Hospital of NY|
|New York, New York, United States|
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|United States, Wisconsin|
|Children's Hopsital of Wisconsin|
|Milwaukee, Wisconsin, United States|
|Principal Investigator:||Sandeep Soni, MD||Nationwide Children's Hospital|