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

NCT02130869 | Completed Phase 1 FDA Drug FDA Device

• 2 other identifiers: ASCISTNCI-2014-00275
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Autologous stem cell transplantation; Natural killer cells

Outcome Measures

Primary Outcomes (1)

• Percent of participants with positive ANC engraftment

  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.

  Day 35 post transplant

Secondary Outcomes (7)

• Overall survival

  Up to one year after transplantation

• Disease-free survival

  Up to one year after transplantation

• Incidence of relapse

  Up to one year after transplantation

• Lymphocyte and hematopoietic reconstitution

  Up to one year after transplantation

• Characteristics of the stem cell grafts

  Up to one year after transplantation

Study Arms (3)

Group A: Neuroblastoma

EXPERIMENTAL

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.

Biological: CD133+ selected autologous stem cell infusion; Biological: IL-2; Biological: hu14.18K322A; Drug: Busulfan; Drug: Melphalan; Biological: GM-CSF; Device: Haploidentical natural killer cell infusion; Biological: G-CSF; Device: CliniMACS

Group B: Lymphoma

EXPERIMENTAL

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.

Biological: CD133+ selected autologous stem cell infusion; Biological: IL-2; Drug: Melphalan; Biological: GM-CSF; Drug: Bendamustine; Drug: Etoposide; Drug: Cytarabine; Device: Haploidentical natural killer cell infusion; Biological: G-CSF; Drug: Etoposide phosphate; Device: CliniMACS

Group C: High-Risk Tumors

EXPERIMENTAL

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.

Biological: CD133+ selected autologous stem cell infusion; Biological: IL-2; Drug: Melphalan; Biological: GM-CSF; Drug: Etoposide; Drug: Carboplatin; Device: Haploidentical natural killer cell infusion; Biological: G-CSF; Drug: Etoposide phosphate; Device: CliniMACS

Interventions

CD133+ selected autologous stem cell infusion BIOLOGICAL

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.

Also known as: Natural killer (NK) cell infusion

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

IL-2 BIOLOGICAL

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.

Also known as: Interleukin-2, Aldesleukin, Proleukin(R)

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

hu14.18K322A BIOLOGICAL

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

Also known as: anti-GD2 antibody, Hu14.18K322MAB

Group A: Neuroblastoma

Busulfan DRUG

Given IV - Group A only.

Also known as: Busulfex(R), Myleran(R)

Group A: Neuroblastoma

Melphalan DRUG

Given IV - All groups.

Also known as: L-phenylalanine mustard, Phenylalanine mustard, L-PAM, L-sarcolysin

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

GM-CSF BIOLOGICAL

Given SQ - All groups.

Also known as: Sargramostim, Leukine(R)

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

Bendamustine DRUG

Given IV - Group B only.

Also known as: Treanda®, Bendamustine hydrochloride

Group B: Lymphoma

Etoposide DRUG

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

Also known as: VP-16, Vepesid(R)

Group B: Lymphoma; Group C: High-Risk Tumors

Cytarabine DRUG

Given IV - Group B only.

Also known as: ARA-C

Group B: Lymphoma

Carboplatin DRUG

Given IV - Group C only.

Also known as: Inorganic heavy metal coordination complex

Group C: High-Risk Tumors

Haploidentical natural killer cell infusion DEVICE

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.

Also known as: NK cell infusion

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

G-CSF BIOLOGICAL

Given SQ - All Groups.

Also known as: Filgrastim, Neupogen(R)

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

Etoposide phosphate DRUG

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

Also known as: Etopophos(R)

Group B: Lymphoma; Group C: High-Risk Tumors

CliniMACS DEVICE

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.

Also known as: Cell Selection System

Group A: Neuroblastoma; Group B: Lymphoma; Group C: High-Risk Tumors

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Less than or equal to 21 years of age.
• Malignancy at high risk of treatment failure for which autologous hematopoietic stem cell transplantation is considered within standard practice.
• Group A: High-risk neuroblastoma
• Group B: Recurrent or refractory Hodgkin lymphoma; recurrent or refractory non-Hodgkin lymphoma
• Group C: High-risk, recurrent or metastatic sarcoma; recurrent or advanced stage Wilms tumor; desmoplastic small round cell tumor; metastatic or recurrent retinoblastoma, high-risk germ cell tumors, and high-risk brain tumors
• Sarcoma or Wilms tumor diagnosis (Group C) will require evaluation by physician in the St. Jude Solid Tumor Division, other than the referring physician, attesting that autologous SCT provides the prospect of direct benefit for the participant.
• Has a potentially suitable human leukocyte antigen (HLA) haploidentical donor available.
• Research participant or legal guardian/representative must be willing to give written informed consent
• Does not have any active or prior malignant or pre-malignant condition of the bone marrow, excluding metastasis of the primary malignancy.
• Has no known allergy to murine products or positive human anti-mouse antibody (HAMA).
• (Female only) Negative serum or urine pregnancy test (to be conducted within 7 days prior to enrollment).
• (Female only) Not breastfeeding.
• Has a confirmed suitable HLA haploidentical donor available.
• Previously collected autologous stem cell product met the minimum collection target and minimum infusion target as described in the protocol.
• At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Neuroblastoma; Lymphoma

Interventions

Interleukin-2; aldesleukin; Hu14.18K322A monoclonal antibody; humanized 3F8 anti-GD2 monoclonal antibody; Busulfan; Melphalan; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Bendamustine Hydrochloride; Etoposide; Cytarabine; Carboplatin; Granulocyte Colony-Stimulating Factor; Filgrastim; etoposide phosphate

Condition Hierarchy (Ancestors)

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; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes

Study Officials

• Brandon M. Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2014
• First Posted: May 6, 2014
• Study Start: October 10, 2014
• Primary Completion: December 20, 2017
• Study Completion: December 20, 2017
• Last Updated: December 22, 2017

Record last verified: 2017-12

Locations

US (1)