Neoplasms

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Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

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Alkylating Agents

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Phenylalanine

All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.

Cells for infusion are prepared using the CliniMACS System.

All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.

Cells for infusion are prepared using the CliniMACS System.

All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.

Cells for infusion are prepared using the CliniMACS System.

Hematopoietic 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.

CD133+ selected autologous stem cell infusion

Following 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.

IL-2

Participants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).

hu14.18K322A

GM-CSF

Bendamustine

Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.

NK 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.

Haploidentical natural killer cell infusion

G-CSF

In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.

The 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.

CliniMACS

Brandon M. Triplett, MD

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.

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

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

Feasibility will be determined based on ANC engraftment defined as ANC ≥500/mm\^3 for 3 consecutive tests performed on different days evaluated before day 35 post-transplant. If the study is considered feasible, the ANC engraftment rate will be 100% (95% Blyth-Still-Casella (BSC) CI: 76.45%-100%) without any failure, 92% (BSC 95% CI: 65.11%-99.57%) with 1 failure, and 83% (BSC 95% CI: 55%-96.95%) with 2 failures. In addition, if more than 2 (≥ 3) on-therapy patients die due to any protocol treatment-related causes during the first 12 months post-transplant across all groups (3 deaths among 36 participants), the study will be stopped. Deaths due to treatment not specified in this protocol will not be included in evaluation of this stopping rule.

Overall survival is defined based on any death. The Kaplan-Meier Estimate will be provided.

Disease-free survival is defined based on any death, graft failure, or relapsed/resistant disease. The Kaplan-Meier Estimate will be provided.

Cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event.

The hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.

Results will be reported and presented descriptively.

The Kaplan-Meier estimate will be provided for overall survival analysis.

Spots Global Cancer Trial Database for cd133+ selected autologous stem cell infusion