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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02650648
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : January 31, 2020
Sponsor:
Collaborator:
Y-mAbs Therapeutics
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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


Condition or disease Intervention/treatment Phase
Neuroblastoma High-Risk Drug: cyclophosphamide Biological: NK cells Biological: hu3F8 Drug: rIL-2 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of the Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Study Start Date : January 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: Humanized Anti-GD2 Antibody Hu3F8
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.
Drug: cyclophosphamide
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).
Other Name: Cytoxan®

Biological: NK cells
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.

Biological: hu3F8
On Days -1, +1, +5, +7 and +9 hu3F8 is administered at 1.68 mg/kg/day and infused over ~30-90 minutes

Drug: rIL-2
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 Measures :
  1. The number patient responses observed at each dose level [ Time Frame: 2 years ]
    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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02650648


Contacts
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Contact: Shakeel Modak, MD 212-639-7623
Contact: Katharine Hsu, MD, PhD 646-888-2667

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Shakeel Modak, MD    212-639-7623      
Contact: Katharine Hsu, MD, PhD    646-888-2667      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Y-mAbs Therapeutics
Investigators
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Principal Investigator: Shakeel Modak, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02650648    
Other Study ID Numbers: 15-272
5415 ( Other Identifier: OPD grant number )
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020
Keywords provided by Memorial Sloan Kettering Cancer Center:
Humanized Anti-GD2 Antibody Hu3F8
Allogeneic Natural Killer Cells
rIL-2
15-272
Additional relevant MeSH terms:
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Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Antibodies
Immunoglobulins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists