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

Primary Purpose

Neuroblastoma, Bone Marrow, Sympathetic Nervous System

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring BETA-D-GLUCAN, CYCLOPHOSPHAMIDE (CYTOXAN), MAB 131 I - 3F8, TOPOTECAN, VINCRISTINE, Neuroblastoma, 09-011

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

chemotherapy, allogeneic NK cells, 3F8

Arm Description

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.

Outcomes

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

Full Information

First Posted
April 6, 2009
Last Updated
January 9, 2019
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00877110
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
April 2, 2009 (Actual)
Primary Completion Date
January 7, 2019 (Actual)
Study Completion Date
January 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Bone Marrow, Sympathetic Nervous System
Keywords
BETA-D-GLUCAN, CYCLOPHOSPHAMIDE (CYTOXAN), MAB 131 I - 3F8, TOPOTECAN, VINCRISTINE, Neuroblastoma, 09-011

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
chemotherapy, allogeneic NK cells, 3F8
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8
Intervention Description
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).
Primary Outcome Measure Information:
Title
Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Estimate the anti-NB effect of allogeneic NK infusions plus 3F8
Time Frame
3 years
Title
Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8
Time Frame
3 years
Title
Assess the relationship between CD16 polymorphism and ADCC in vitro
Time Frame
3 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shakeel Modak, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

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

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