Allogeneic Stem Cell Transplantation for Advanced Neuroblastoma Using MHC Mismatched Related Donors (STALLO)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.

Verified February 2015 by Children's Mercy Hospital Kansas City.
Recruitment status was: Active, not recruiting

Sponsor:

Collaborator:

University of Kansas

Information provided by (Responsible Party):

Children's Mercy Hospital Kansas City

ClinicalTrials.gov Identifier:

NCT01462396

First received: October 25, 2011

Last updated: February 4, 2015

Last verified: February 2015

History of Changes

Purpose

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.

Condition	Intervention	Phase
Neuroblastoma	Device: CD34+ cells selected with the Miltenyi Clinimacs machine	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Phase I Study of Allogeneic Stem Cell Transplantation for Advanced Neuroblastoma Using Major Histocompatibility Complex (MHC) Mismatched Related Donors and Sub-Myeloablative Regimen

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

MedlinePlus related topics: Neuroblastoma

Genetic and Rare Diseases Information Center resources: Neuroblastoma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Children's Mercy Hospital Kansas City:

Primary Outcome Measures:

The immediate safety of a fludarabine based reduced intensity conditioning regimen and CD34+ stem cell selected mis-matched, related, allogeneic transplant will be assess in patients with relapsed/refractory neuroblastoma [ Time Frame: 6 weeks ]
Monitoring of mortality, toxicity (NCI Common Criteria), acute and chronic graft versus host disease, engraftment rate will contribute to safety assessment

Secondary Outcome Measures:

Infusional and long term safety and persistence of tumor redirected, genetically modified, donor derived, allogeneic multi-virus specific cytotoxic T-cells (tV-CTL) after allogeneic hematopoietic stem cell transplant in patients with neuroblastoma [ Time Frame: 4-8 weeks post transplant ]
Tumor evaluation will occur 4-8 weeks after transplant


Estimated Enrollment:	10
Study Start Date:	October 2011
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Intervention Details:

Haploidentical allogeneic stem cell transplant following sub-myeloablative conditioning and cell selection using the Miltenyi Clinimacs device

Eligibility


Ages Eligible for Study:	6 Months to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462396

Locations


United States, Missouri
Children's Mercy Hospital
Kanas City, Missouri, United States, 64108

Sponsors and Collaborators

Children's Mercy Hospital Kansas City

University of Kansas

More Information

Additional Information:

Children's Mercy Hospital This link exits the ClinicalTrials.gov site


Responsible Party:	Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier:	NCT01462396 History of Changes
Other Study ID Numbers:	STALLO
Study First Received:	October 25, 2011
Last Updated:	February 4, 2015

Keywords provided by Children's Mercy Hospital Kansas City:


Neuroblastoma Relapsed Refractory

Additional relevant MeSH terms:


Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors	Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 23, 2017

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