Neuroblastoma Recurrent Clinical Trial
Official title:
Pilot Study of Anti-GD2 and Expanded, Activated Natural Killer Cell Infusion for Neuroblastoma
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).
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