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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.

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

Miriam Kimpo, MD

Chetan Dhamne, MBBS, MS, MD

Dr. Miriam Kimpo, MD

Dr.Chetan Dhamne, MBBS, MS. MD

Dario Campana, MD, PhD

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.

Adoptive transfer of haploidentical NK cells has been shown to be safe in clinical trials at NUH. There is experience combining antibody infusion with autologous NK cells in the clinical trial with good safety data.

The proposed trial is a phase I/II study to determine the safety and efficacy of expanded activated haploidentical NK cells in combination with anti-GD2 (ch14.18/CHO). We plan to enrol patients with high risk or relapsed neuroblastoma with evidence of residual disease who are at high risk of recurrence or progression on current treatment.

In the proposed protocol , we plan to infuse NK cells at escalating dose levels to find the optimum dose tolerated by the patients in combination with anti-GD2 (ch14.18/CHO) . There are 3 NK cell dose levels :

Dose level 1 (1 x 10\^6/kg) , Dose level 2 (1 x 10\^7/kg) , Dose level 3 (1 x 10\^8/kg)

If a partial response or stable disease is observed, further infusions of NK cells can be administered. There will be intra- and inter - patient dose escalation.

The donor will be either parent, based on the best NK cell donor as determined by the study team. The donor will be harvested and NK cells expanded prior to infusion into the patient along with anti-GD2 (ch14.18/CHO).

The study aims to study safety and efficacy of a combination of NK cells and anti-GD2 (ch14.18/CHO).

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

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

Pilot Study of Anti-GD2 and Expanded, Activated Natural Killer Cell Infusion for Neuroblastoma

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).

NK cells will be identified by flow cytometry in peripheral blood and their percentages and absolute numbers will be calculated.

Cytokine panel to assess levels of IL15 serially post lymphodepletion regimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immunotherapy of Neuroblastoma Patients Using a Combination of Anti-GD2 and NK Cells	NCT03242603	Neuroblastoma R...	Anti-GD2 in com...	6 Months - 25 Years	National University Hospital, Singapore
Immunotherapy of Neuroblastoma Patients Using a Combination of Anti-GD2 and NK Cells	NCT03242603	Neuroblastoma R...	Anti-GD2 in com...	6 Months - 25 Years	National University Hospital, Singapore

Spots Global Cancer Trial Database for relapsed, refractory, neuroblastoma