Clinical Trials /

Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

NCT02650648

Description:

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

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk <span class="go-doc-concept go-doc-disease">Neuroblastoma</span>

Title

  • Brief Title: 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
  • Clinical Trial IDs

    NCT ID: NCT02650648

    ORG ID: 15-272

    Trial Conditions

    Neuroblastoma

    High-Risk

    Trial Interventions

    Drug Synonyms Arms
    cyclophosphamide Cytoxan Humanized Anti-GD2 Antibody Hu3F8
    rIL-2 Humanized Anti-GD2 Antibody Hu3F8

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Humanized Anti-GD2 Antibody Hu3F8 Experimental This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with hu3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups with a minimum of 3 patients/ dose of NK cells. Three dose levels of NK cells, starting at dose level 1, will be evaluated in this treatment protocol, as summarized below (Table 1). The goal dose for each dose level is the high boundary (e.g. 9.9x106/kg in level 1; 14.9x106/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved. cyclophosphamide, rIL-2

    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 HAHA antibody titer 1300 Elisa units/ml.
    Human anti-mouse antibody 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 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

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    The number patient responses observed at each dose level

    Secondary Outcome Measures

    Trial Keywords

    Humanized Anti-GD2 Antibody Hu3F8

    Allogeneic Natural Killer Cells

    rIL-2

    15-272