Donor Natural Killer Cells and Hu3F8 in Treating Patients with High-Risk Neuroblastoma
- Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the Memorial Sloan Kettering Cancer Center [MSKCC] Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
- High-risk NB as defined by risk-related treatment guidelines' and the International NB Staging System, i.e., stage 4 with (any age) or without (> 18 months of age) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage 4S
- Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy
- Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive metaiodobenzylguanidine [MIBG] or positron emission tomography [PET] scans) or measurable (computed tomography [CT], magnetic resonance imaging MRI]) disease documented after completion of prior systemic therapy
- Disease staging approximately within one month of treatment
- Prior treatment with murine and hu3F8 is allowed; patients with prior humanizing murine IgG3 anti-GD2 antibody m3F8 (m3F8), hu3F8, ch14.18 or hu14.18 treatment must have human anti-human antibody (HAHA) antibody titer =< 1300 enzyme-linked immunosorbent assay (ELISA) units/ml; human anti-mouse antibody positivity is allowed
- Eligible NK donor
- Signed informed consent indicating awareness of the investigational nature of this program
- DONOR: Donor is blood-related and HLA-haploidentical to the recipient
- DONOR: Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors; tests include but are not limited to: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis C antibody, Epstein-Barr virus antibody, human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV) I and II, varicella zoster (herpes zoster), herpes simplex antibody, cytomegalovirus antibodies, syphilis (rapid plasma reagin [RPR] profile) for adolescents and adults, measles for pediatric patients, West Nile virus, Chagas screen, and toxoplasma antibodies; donor must have normal negative test results for HIV, HTLV I and II, and West Nile virus; donor exposure to other viral pathogens will be discussed on a case-by-case basis by investigators
- DONOR: Donor must be able to undergo leukapheresis for total volume of 10-15 liters
- DONOR: There is no age restriction for the donor
- Patients with complete response (CR)/very good partial response (VGPR) disease
- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity >= grade 3 except for hearing loss, alopecia, anorexia, nausea, hyperbilirubinemia and hypomagnesemia from total parenteral nutrition (TPN), which may be grade 3
- Absolute neutrophil count (ANC) should be > 500/uL
- Platelet count > 75 K/uL
- History of allergy to mouse proteins
- Active life-threatening infection
- Inability to comply with protocol requirements
- Women who are pregnant or breast-feeding
- DONOR: Cardiac risk factors precluding ability to undergo leukapheresis
- DONOR: Concurrent malignancy or autoimmune disease
- DONOR: Donor is pregnant
I. Find the maximum tolerated dose (MTD) of allogeneic haploidentical natural killer (NK) cell infusions with hu3F8 in patients with high-risk neuroblastoma (NB).
I. Estimate the anti-NB effect of allogeneic NK infusions plus hu3F8.
II. Assess the impact of killer immunoglobulin (Ig)-like receptors (KIR)/human leukocyte antigen (HLA) immunogenetics on disease response to NK/hu3F8.
III. Assess the relationship between cluster of differentiation (CD)16 polymorphism and antibody-dependent cellular cytotoxicity (ADCC) in vitro.
IV. Estimate hu3F8 pharmacokinetics.
V. Apply real-time quantitative reverse-transcript-polymerase chain reaction (qRT-PCR) to test the hypothesis that minimal residual disease (MRD) findings in cell free deoxyribonucleic acid (DNA) (cfDNA) and cell free ribonucleic acid (RNA) (cfRNA) after the first 2 cycles of hu3F8 has significant prognostic impact on outcome.
OUTLINE: This is a dose-escalation study of allogeneic NK cells.
CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 6 hours on days -6 and -5.
Hu3F8 INFUSION: Patients receive humanized monoclonal antibody 3F8 IV over 30-90 minutes on days -1, 1, 5, 7, and 9.
NK INFUSION: Patients receive allogeneic NK cells IV on day 0.
ALDESLEUKIN: Patients receive aldesleukin subcutaneously (SC) on days 0, 2-4, 6, and 8.
Treatment may repeat for up to 2 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 2, 3, 6, and 12 months.
Trial Phase Phase I
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
- Primary ID 15-272
- Secondary IDs NCI-2016-00064, 5415
- Clinicaltrials.gov ID NCT02650648