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

Primary Purpose

Neuroblastoma, High-Risk

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
NK cells
hu3F8
rIL-2
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 Humanized Anti-GD2 Antibody Hu3F8, Allogeneic Natural Killer Cells, rIL-2, 15-272

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Humanized Anti-GD2 Antibody Hu3F8

Arm Description

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. The goal dose for each dose level is the high boundary (e.g. 9.9x10^6/kg in level 1; 14.9x10^6/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved.

Outcomes

Primary Outcome Measures

The number patient responses observed at each dose level
as defined by International NB Response Criteria. Disease status is defined by the International NB Response Criteria. Complete response/remission (CR): no evidence of disease. Very good partial response/remission (VGPR): >90% decrease in all disease parameters, except bone scan unchanged or improved; bone marrow must be free of disease. Partial response/remission: >50% decrease in all disease parameters, except bone scan unchanged or improved; no more than 1 positive bone marrow site. Mixed response: >50% decrease in >1 but not all disease markers. Stable disease: <50% decrease in all tumor markers. Progressive disease: new lesion, or >25 % increase in any disease marker.

Secondary Outcome Measures

Full Information

First Posted
January 6, 2016
Last Updated
February 14, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Y-mAbs Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02650648
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (undefined)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Y-mAbs Therapeutics

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, High-Risk
Keywords
Humanized Anti-GD2 Antibody Hu3F8, Allogeneic Natural Killer Cells, rIL-2, 15-272

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Humanized Anti-GD2 Antibody Hu3F8
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 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. The goal dose for each dose level is the high boundary (e.g. 9.9x10^6/kg in level 1; 14.9x10^6/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan®
Intervention Description
chemotherapy with intravenous (IV) cyclophosphamide 50mg/kg/day (for patients with body weight<70kg) or 1500mg/m^2/day (for patients with body weight ≥70kg) for two days (days -6 and -5).
Intervention Type
Biological
Intervention Name(s)
NK cells
Intervention Description
Day 0: NK cell infusion. NK cells are resuspended in Normasol at a concentration no less than 5 x 10^6cells/mL. The patient is pre-medicated as per standard cell product infusion. The cell product is infused through a central venous catheter. Patients will be evaluated clinically by vital signs pre- and approximately 30 minutes post infusion of NK cells and thereafter at approximately 1 hour intervals for 4 hours.
Intervention Type
Biological
Intervention Name(s)
hu3F8
Intervention Description
On Days -1, +1, +5, +7 and +9 hu3F8 is administered at 1.68 mg/kg/day and infused over ~30-90 minutes
Intervention Type
Drug
Intervention Name(s)
rIL-2
Intervention Description
On day 0, daily from +2 through +4, day +6, and day +8, rIL-2 is administered subcutaneously at 6 x 10^5 U/m^2/day.
Primary Outcome Measure Information:
Title
The number patient responses observed at each dose level
Description
as defined by International NB Response Criteria. Disease status is defined by the International NB Response Criteria. Complete response/remission (CR): no evidence of disease. Very good partial response/remission (VGPR): >90% decrease in all disease parameters, except bone scan unchanged or improved; bone marrow must be free of disease. Partial response/remission: >50% decrease in all disease parameters, except bone scan unchanged or improved; no more than 1 positive bone marrow site. Mixed response: >50% decrease in >1 but not all disease markers. Stable disease: <50% decrease in all tumor markers. Progressive disease: new lesion, or >25 % increase in any disease marker.
Time Frame
2 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
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
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

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

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