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:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • ORG STUDY ID: 15-272
  • SECONDARY ID: 5415
  • NCT ID: NCT02650648

Conditions

  • Neuroblastoma
  • High-Risk

Interventions

DrugSynonymsArms
cyclophosphamideCytoxan®Humanized Anti-GD2 Antibody Hu3F8
NK cellsHumanized Anti-GD2 Antibody Hu3F8
hu3F8Humanized Anti-GD2 Antibody Hu3F8
rIL-2Humanized Anti-GD2 Antibody Hu3F8

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. Funding Source- FDA OOPD

Trial Arms

NameTypeDescriptionInterventions
Humanized Anti-GD2 Antibody Hu3F8ExperimentalThis 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.
  • cyclophosphamide
  • NK cells
  • hu3F8
  • 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:The number patient responses observed at each dose level
Time Frame:2 years
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Humanized Anti-GD2 Antibody Hu3F8
  • Allogeneic Natural Killer Cells
  • rIL-2
  • 15-272

Last Updated

September 17, 2020