Clinical Trials /

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

NCT00877110

Description:

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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Anti-GD2 3F8 <span class="go-doc-concept go-doc-intervention">Antibody</span> and Allogeneic Natural Killer Cells for High-Risk <span class="go-doc-concept go-doc-disease">Neuroblastoma</span>

Title

  • Brief Title: 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
  • Clinical Trial IDs

    NCT ID: NCT00877110

    ORG ID: 09-011

    NCI ID: MSKCC09011 FDR004128

    Trial Conditions

    Neuroblastoma

    Bone Marrow, Sympathetic Nervous System

    Trial Interventions

    Drug Synonyms Arms
    cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8 chemotherapy, allogeneic NK cells, 3F8

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    chemotherapy, allogeneic NK cells, 3F8 Experimental This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with 3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups of 3 patients/dose of NK cells. Four dose levels of NK cells, starting at dose level I, will be evaluated in this treatment protocol. In the unlikely case toxicity is encountered at dose level I, patients will then be treated at the lower dose level 0. Patients can receive up to 3 cycles of treatment on protocol. For subsequent cycles, patients will be treated at either less than or at the same dose level of NK cells as their first cycle. cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8

    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.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB

    Secondary Outcome Measures

    Estimate the anti-NB effect of allogeneic NK infusions plus 3F8

    Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8

    Assess the relationship between CD16 polymorphism and ADCC in vitro

    Trial Keywords

    BETA-D-GLUCAN

    CYCLOPHOSPHAMIDE (CYTOXAN)

    MAB 131 I - 3F8

    TOPOTECAN

    VINCRISTINE

    Neuroblastoma

    09-011