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

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.

Conditions

• Neuroblastoma
• Lymphoma
• High-risk Tumor

Interventions

BIOLOGICAL

CD133+ selected autologous stem cell infusion

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.

BIOLOGICAL

IL-2

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.

BIOLOGICAL

hu14.18K322A

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

DRUG

Busulfan

Given IV - Group A only.

DRUG

Melphalan

Given IV - All groups.

BIOLOGICAL

GM-CSF

Given SQ - All groups.

DRUG

Bendamustine

Given IV - Group B only.

DRUG

Etoposide

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

DRUG

Cytarabine

Given IV - Group B only.

DRUG

Carboplatin

Given IV - Group C only.

DEVICE

Haploidentical natural killer cell infusion

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.

BIOLOGICAL

G-CSF

Given SQ - All Groups.

DRUG

Etoposide phosphate

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

DEVICE

CliniMACS

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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Brandon M. Triplett, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-10-10

Primary Completion

2017-12-20

Completion

2017-12-20

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations