Clinical trial NCT02650648: Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Official title: Phase I Study of the Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Neuroblastoma
High-Risk
Keywords: Humanized Anti-GD2 Antibody Hu3F8
Allogeneic Natural Killer Cells
rIL-2
15-272
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Y-mAbs Therapeutics
First posted: 2016-01-08
Enrollment: 85
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I study. The purpose of this study is to see if it is safe and feasible to give the participant cyclophosphamide (a type of chemotherapy), natural killer (NK) cells, and an antibody called Hu3F8 as a treatment for neuroblastoma. NK cells are a type of white blood cell.

Funding Source- FDA OOPD


Eligibility criteria: Inclusion Criteria:

* Diagnosis of NB as defined by international criteria,.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 guidelines1 and the International NB Staging System, 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
* Prior treatment with murine and hu3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody (HAMA) positivity is allowed.
* Eligible NK donor
* Children and adults are eligible
* Signed informed consent indicating awareness of the investigational nature of this program.

Donor Inclusion Criteria

* 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: Hepatitis B Surface Antigen, Hepatitis B Surface Antibody, Hepatitis B Core Antibody, Hepatitis C antibody, Epstein-Barr Virus Antibody, HIV, HTLV I and II, Varicella Zoster (Herpes Zoster), Herpes Simplex Antibody, Cytomegalovirus Antibodies, Syphilis (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 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 \> 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 \>75K/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 Exclusion Criteria:

* Cardiac risk factors precluding ability to undergo leukopheresis
* Concurrent malignancy or autoimmune disease
* Donor is pregnant

Primary outcomes:
measure: The number patient responses observed at each dose level
timeFrame: 2 years
Secondary outcomes:
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: