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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2011 by Children's Mercy Hospital Kansas City
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: October 27, 2011
Last verified: October 2011
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:


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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Tumor evaluation will occur 4-8 weeks after transplant


Estimated Enrollment: 10
Study Start Date: October 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: CD34+ cells selected with the Miltenyi Clinimacs machine
    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
Genders Eligible for Study:   Both
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

Contacts
Contact: Doug Myers, MD 816-234-3265 gdmyers@cmh.edu
Contact: Robin Ryan, MPH 816-802-1474

Locations
United States, Missouri
Children's Mercy Hospital Recruiting
Kanas City, Missouri, United States, 64108
Contact: Doug Myers, MD    816-234-3265    gdmyers@cmh.edu   
Contact: Robin Ryan, MPH    816-802-1474    rryan@cmh.edu   
Principal Investigator: Doug Myers, MD         
Sub-Investigator: Jignesh Dalal, MD         
Sub-Investigator: Carla McCrave, MD         
Sub-Investigator: Mohamed Radhi, MD         
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
University of Kansas
  More Information

Additional Information:
No publications provided

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: October 27, 2011
Health Authority: United States: Food and Drug Administration

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 19, 2014