Allogeneic Stem Cell Transplantation for Advanced Neuroblastoma Using MHC Mismatched Related Donors
| Status: | Completed |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 17 |
| Updated: | 7/20/2018 |
| Start Date: | October 2011 |
| End Date: | December 2015 |
Phase I Study of Allogeneic Stem Cell Transplantation for Advanced Neuroblastoma Using Major Histocompatibility Complex (MHC) Mismatched Related Donors and Sub-Myeloablative Regimen
Allogeneic stem cell transplantation has been explored for patients with high risk
neuroblastoma. Results have been mixed, with only small series and case reports. Recent
reports, however, especially with haploidentical transplantation have been more encouraging.
Eradication of neuroblastoma may be mediated by both components of the innate immune system
(natural killer cells) and through the adaptive immune system via T-cell cytotoxicity and the
development of a humoral response to tumor specific antigens and minor histocompatibility
antigens. To overcome restrictions created by unavailability of Human leukocyte antigen (HLA)
matched donors, stem cell grafts from haploidentical related donors have been explored.
Historically, the use of full haplotype mismatched family member donors has been limited by
the development of severe graft-versus-host disease and the high rate of graft failure. Graft
failure can now be overcome by increasing immunosuppression and increasing the number of
transplanted stem cells. The most effective means of graft versus host disease (GVHD)
prophylaxis is T cell depletion of the donor marrow. A 3-4 log depletion will reduce the risk
of developing significant GVHD to less than 10%. Methods to mobilize stem cells from the bone
marrow into the peripheral blood and collect these stem cells by apheresis now increase the
availability of stem cells by a magnitude. Selection devices have been developed that will
prepare extremely pure populations of these CD34 cells with upwards of 5 logs depletion of
contaminating T cells. The CliniMACS CD34 Reagent System is a medical device designed to
select CD34+ hematopoietic cells from heterogeneous hematologic cell populations. The
investigators intend to provide mismatched related hematopoietic stem cell transplantation to
up to 10 patients with relapsed refractory neuroblastoma. Harnessing the potential for innate
and adaptive immune responses through allogeneic Hematopoietic stem cell transplantation
(HSCT) may provide cure for some patients with this tumor.
neuroblastoma. Results have been mixed, with only small series and case reports. Recent
reports, however, especially with haploidentical transplantation have been more encouraging.
Eradication of neuroblastoma may be mediated by both components of the innate immune system
(natural killer cells) and through the adaptive immune system via T-cell cytotoxicity and the
development of a humoral response to tumor specific antigens and minor histocompatibility
antigens. To overcome restrictions created by unavailability of Human leukocyte antigen (HLA)
matched donors, stem cell grafts from haploidentical related donors have been explored.
Historically, the use of full haplotype mismatched family member donors has been limited by
the development of severe graft-versus-host disease and the high rate of graft failure. Graft
failure can now be overcome by increasing immunosuppression and increasing the number of
transplanted stem cells. The most effective means of graft versus host disease (GVHD)
prophylaxis is T cell depletion of the donor marrow. A 3-4 log depletion will reduce the risk
of developing significant GVHD to less than 10%. Methods to mobilize stem cells from the bone
marrow into the peripheral blood and collect these stem cells by apheresis now increase the
availability of stem cells by a magnitude. Selection devices have been developed that will
prepare extremely pure populations of these CD34 cells with upwards of 5 logs depletion of
contaminating T cells. The CliniMACS CD34 Reagent System is a medical device designed to
select CD34+ hematopoietic cells from heterogeneous hematologic cell populations. The
investigators intend to provide mismatched related hematopoietic stem cell transplantation to
up to 10 patients with relapsed refractory neuroblastoma. Harnessing the potential for innate
and adaptive immune responses through allogeneic Hematopoietic stem cell transplantation
(HSCT) may provide cure for some patients with this tumor.
Inclusion Criteria:
- Age 6 months - <18 years
- Measurable tumor by routine imaging or bone marrow biopsy
- Patient must have an 3/6, 4/6, or 5/6 human leukocyte antigen (HLA)-mismatched related
donor who is Epstein-Barr virus (EBV) seropositive
- Karnofsky score 60% or greater if 10yrs old or older, Lansky score 60% or greater if
under 10yrs old
- Pulse ox >90% on room air
- Recovered from toxic effects of prior chemotherapy
- Patient must not be pregnant
- Patient must be HIV negative
- Patient or responsible person must be able to understand and sign an informed consent
- Available donor without contraindication for stem cell collection
Exclusion Criteria:
- Pregnant and lactating women.
- Human immunodeficiency virus (HIV) positive patient.
- Uncontrolled intercurrent infection.
- Renal failure (Creatine > 1.5 or Creatinine Clearance < 40 ml/min/1.73m2)
- Active hepatitis or cirrhosis with liver test values greater than 3 times normal
- NOTE: Patients who would be excluded from the protocol strictly for laboratory
abnormalities can be included at the investigator's discretion, after review by the
Children's Mercy Hospital ethics board
- Donor Inclusion/Exclusion Criteria
- Donor must be in good health based on review of systems and results of physical
examination, and routine testing per standards of good medical care.
- Female donors of childbearing age must have a negative pregnancy test and must not be
lactating
- EBv seropositive
- Donor stem cells should be human leukocyte antigen (HLA) typed using molecular
methods. See section 6.1.3 for HLA matching requirements.
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