Clinical trial NCT00877110: Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Official title: Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Bone Marrow, Sympathetic Nervous System
Keywords: BETA-D-GLUCAN
CYCLOPHOSPHAMIDE (CYTOXAN)
MAB 131 I - 3F8
TOPOTECAN
VINCRISTINE
Neuroblastoma
09-011
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2009-04-07
Enrollment: 71
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB
timeFrame: 3 years
Secondary outcomes:
measure: Estimate the anti-NB effect of allogeneic NK infusions plus 3F8
timeFrame: 3 years
measure: Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8
timeFrame: 3 years
measure: Assess the relationship between CD16 polymorphism and ADCC in vitro
timeFrame: 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Shakeel Modak, MD
role: PRINCIPAL_INVESTIGATOR
References: