Immunotherapy of Neuroblastoma Patients Using a Combination of Anti-GD2 and NK Cells

NCT03242603 | Unknown Phase 1

• 1 other identifier: NKEXPGD2
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroblastoma is a neoplasm of the sympathetic nervous system which affects mostly children younger than 5 years of age. It is a heterogeneous disease, with nearly 50% of patients presenting with a high-risk phenotype. After standard treatment, the 2-year event-free survival (EFS) for high risk neuroblastoma (EFS) is only about 50%. Immunotherapy with anti-GD2 antibodies has been shown to improve EFS in Children's Oncology Group and SIOPEN trials. The anti-GD2 antibody mediates neuroblastoma cell killing primarily through antibody-dependent cell-mediated cytotoxicity (ADCC). Natural killer (NK) cells are the main effectors of ADCC. We postulate that infusion of expanded activated NK cells from healthy haploidentical donors along with anti-GD2 antibody will enhance neuroblastoma killing.

Conditions

Neuroblastoma Recurrent

Keywords

Relapsed, Refractory, Neuroblastoma; Anti-GD2; Natural Killer (NK) Cells; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• To measure tumor response after infusion of expanded activated haploidentical NK cells with anti-GD2. Response will be assessed as defined by Revised International Neuroblastoma Response Criteria 2017.

  Disease status at primary and metastatic soft tissue sites will be assessed using MIBG scans or PET scan as applicable. RECIST and Curie scoring systems will be used to assess response. Metastatic bone disease will be assessed using MIBG or PET scan. Bone marrow will be assessed by histology or flow cytometry. Disease response will be defined as Complete response/remission (CR), Partial response (PR), Minor response, Stable disease (SD), or Progressive disease(PD).

  2 years

Secondary Outcomes (2)

• To measure the numbers of infused NK cells in peripheral blood at specific time-points after NK cell infusion

  2 years

• To measure cytokine levels in plasma at specific time-points after NK cell infusion

  2 years

Study Arms (1)

Anti-GD2 in combination with NK cells

EXPERIMENTAL

This is a single arm study. Patients with high risk neuroblastoma who have residual measurable disease will receive a combination of 5 days of anti-GD2 with expanded activated NK cells.

Biological: Anti-GD2 in combination with NK cells

Interventions

Anti-GD2 in combination with NK cells BIOLOGICAL

Haploidentical donor NK cells will be expanded over 10 days and infused in combination with anti-GD2. Anti-GD2 will be given as daily infusion for 5 days ; D-1, 0,+1, +2 and +3. NK cells will be infused at single dose on day 0. The patient will receive cyclophosphamide 60mg/kg on day -3 and day -2 prior to the NK cell infusion. IL- 2 will be given subcutaneously for 6 doses every alternate day starting on day -1, for NK cell survival.

Anti-GD2 in combination with NK cells

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 6 months to 25 years old.
• Patients with high risk or relapsed neuroblastoma who have measurable residual disease (based on imaging findings with Curie scoring or MIBG or PET imaging criteria) after receiving or has refused to receive standard therapy.
• High risk will be defined as stage IV disease with poor response to chemotherapy. Residual disease after surgery or prior to autologous stem cell rescue which is part of Standard of Care. Infants with nMYC amplification will not automatically qualify for the protocol unless they have residual disease after surgery.
• Recurrence after completion of standard treatment.
• Shortening fraction greater than or equal to 25% or Left ventricular ejection fraction (LVEF) greater than or equal to 40%.
• Glomerular filtration rate greater than or equal to 60 ml/min/1.73 m2.
• Pulse oximetry greater than or equal to 92% on room air.
• Direct bilirubin less than or equal to 3.0 mg/dL (50 mmol/L).
• Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.
• Aspartate transaminases (AST) is no more than 2 times the upper limit of normal.
• Karnofsky or Lansky performance score of greater than or equal to 50.
• Does not have a current pleural or pericardial effusion.
• Has a suitable adult family member donor available for NK cell donation.
• Has recovered from all acute NCI Common Terminology Criteria for Adverse Events (CTCAE) grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the PI.
• At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.

You may not qualify if:

• Failure to meet any of the above criteria

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Related Publications (3)

• Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123.

  PMID: 20879881 BACKGROUND

• Cho D, Shook DR, Shimasaki N, Chang YH, Fujisaki H, Campana D. Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin Cancer Res. 2010 Aug 1;16(15):3901-9. doi: 10.1158/1078-0432.CCR-10-0735. Epub 2010 Jun 11.

  PMID: 20542985 BACKGROUND

• Tarek N, Le Luduec JB, Gallagher MM, Zheng J, Venstrom JM, Chamberlain E, Modak S, Heller G, Dupont B, Cheung NK, Hsu KC. Unlicensed NK cells target neuroblastoma following anti-GD2 antibody treatment. J Clin Invest. 2012 Sep;122(9):3260-70. doi: 10.1172/JCI62749. Epub 2012 Aug 6.

  PMID: 22863621 BACKGROUND

MeSH Terms

Conditions

Recurrence; Neuroblastoma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Study Officials

• Miriam Kimpo, MD

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

• Dario Campana, MD, PhD

  National University Singapore, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miriam Kimpo, MD

CONTACT

+65 8494 3914; miriam_kimpo@nuhs.edu.sg

Chetan Dhamne, MBBS, MS, MD

CONTACT

+65 6772 3361; chetan_dhamne@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To determine the feasibility, safety and effectiveness of anti-GD2 in combination with expanded, activated NK cells in research participants with Neuroblastoma

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: August 8, 2017
• Study Start: October 3, 2017
• Primary Completion: August 15, 2019
• Study Completion: August 15, 2020
• Last Updated: March 30, 2018

Record last verified: 2017-06

Locations

SG (1)