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CompletedNCT02130869

A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
8 (actual)
Sponsor
St. Jude Children's Research Hospital · Academic / Other
Sex
All
Age
21 Years
Healthy volunteers
Not accepted

Summary

This is a pilot clinical trial investigating the addition of haploidentical natural killer cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. Natural killer cells from a haploidentical family member will be given after high dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined. The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.

Detailed description

Primary Objective: * To evaluate day +35 ANC engraftment in autologous stem cell transplantation for high risk pediatric malignancies after stem cell selection and immunotherapy. Secondary Objectives * To estimate incidence of relapse, disease-free survival and overall survival. * To characterize lymphocyte and hematopoietic reconstitution in these patients. * To describe the characteristics of the stem cell and natural killer cell grafts. * To estimate the overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria

Conditions

Interventions

TypeNameDescription
BIOLOGICALCD133+ selected autologous stem cell infusionHematopoietic stem cells will be collected from children with high-risk solid tumors. After collection, they will be immuno-magnetically selected using CD133 as a marker in efforts to reduce tumor cell contamination in the stem cell graft. After high dose chemotherapy, those selected stem cells will be infused, followed shortly thereafter by an infusion of haploidentical natural killer cells.
BIOLOGICALIL-2Following infusion of haploidentical natural killer cells, interleukin-2 (IL-2) subcutaneously (SQ) will be given to support the in vivo survival of donor NK cells.
BIOLOGICALhu14.18K322AParticipants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).
DRUGBusulfanGiven IV - Group A only.
DRUGMelphalanGiven IV - All groups.
BIOLOGICALGM-CSFGiven SQ - All groups.
DRUGBendamustineGiven IV - Group B only.
DRUGEtoposideGiven IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
DRUGCytarabineGiven IV - Group B only.
DRUGCarboplatinGiven IV - Group C only.
DEVICEHaploidentical natural killer cell infusionNK cell product will be collected from donors using leukapheresis procedures. The autologous hematopoietic stem cell graft product will be positively selected using the investigational CliniMACS device and CD133 Microbead reagent. Following standard laboratory procedures, the NK cell product will be enumerated and assessed for viable cell content. NK cells will be infused by slow IV push over 3 to 15 minutes immediately after processing, evaluation and release testing.
BIOLOGICALG-CSFGiven SQ - All Groups.
DRUGEtoposide phosphateIn case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
DEVICECliniMACSThe mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Timeline

Start date
2014-10-10
Primary completion
2017-12-20
Completion
2017-12-20
First posted
2014-05-06
Last updated
2017-12-22

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT02130869. Inclusion in this directory is not an endorsement.