Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877110
• Other study ID #: 09-011
• Secondary ID: MSKCC09011 FDR00
• Status: Completed
• Phase: Phase 1
• Start date: April 2, 2009
• Est. completion date: January 7, 2019

Study information

• Verified date: January 2019
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Funding Source - FDA OOPD FDR004128

The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who shares half of the HLA proteins which are immune proteins important in transplant. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body and can work together with antibodies to kill target cells. The antibody 3F8 specifically recognizes a protein present on the target cancer cell.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: January 7, 2019
• Est. primary completion date: January 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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 catecholamine levels

• 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 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 MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.

• Disease staging approximately 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 program.

Donor Eligibility

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Bone Marrow, Sympathetic Nervous System
• Neuroblastoma

Intervention

Drug:
• cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8
Patients will receive combination chemotherapy with intravenous (IV) cyclophosphamide 70mg/kg/day (for patients with body weight<70kg) or 2100mg/m2/day (for patients with body weight =70kg) for two days, IV vincristine 0.067mg/kg or 2mg/m2/day (lower of the two doses to be chosen; maximum 2mg) for one day, and IV topotecan 2.4 mg/m2/day for 3 days during their first cycle. If receiving a second and/or third cycle, the only chemotherapy patients will receive is cyclophosphamide at 50 mg/kg/day for 2 days. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor. On day +3, the patient will start daily infusion of 3F8 for 5 days. The treatment schedule may require minor adjustment by ±1 day as clinically indicated (e.g. due to PDH closure for holidays or due to inclement weather).

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB		3 years
Secondary	Estimate the anti-NB effect of allogeneic NK infusions plus 3F8		3 years
Secondary	Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8		3 years
Secondary	Assess the relationship between CD16 polymorphism and ADCC in vitro		3 years

External Links

•   Memorial Sloan Kettering Cancer Center