Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
- Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed
by the MSKCC Department of Pathology) or bone marrow metastases plus high urine
- High-risk NB as defined by risk-related treatment guidelines and the International NB
Staging System,57 i.e., stage 4 with (any age) or without (>365 days of age) MYCN
amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified
- 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 MIBG or PET scans) or measurable (CT, MRI) disease documented after
completion of prior systemic therapy.
- Disease staging within one month of treatment.
- Human anti-mouse antibody (HAMA) titer <1000 Elisa units/ml if applicable
- Available autologous stem cells: ≥2 x 106 CD34+ cells/kg
- Adequate cardiac function as measured by echocardiogram
- Eligible NK donor
- Signed informed consent indicating awareness of the investigational nature of this
- Donor is blood-related and HLA-haploidentical to the recipient.
- 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:
HepBsAg, HepBsAb, HepBcAb, HepC antibody, HIV, HTLV I and II, VZV, CMV and VDRL, West
Nile Virus and Chagas screen. 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 the investigators.
- Donor must be able to undergo leukopheresis for total volume of 10-15 liters.
- There is no age restriction for the donor.
- Patients with CR/VGPR disease
- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic,
pulmonary, or gastrointestinal toxicity > or = to grade 3 except for hearing loss,
alopecia, anorexia, nausea, hyperbilirubinemia and hypomagnesemia from TPN, which
may be grade 3
- ANC should be >500/uL; platelet count >25K/uL.
- History of allergy to mouse proteins
- Active life-threatening infection
- HAMA titer >1000 Elisa units/ml
- Inability to comply with protocol requirements
Donor Exclusion Criteria
- Cardiac risk factors precluding ability to undergo leukopheresis
- Concurrent malignancy or autoimmune disease
- Donor is pregnant.