A Safety/Feasibility Trial of the Addition of the Humanized Anti-GD2 Antibody (hu14.18K322A) With and Without Natural Killer Cells to Chemotherapy in Children and Adolescents With Recurrent/Refractory Neuroblastoma (GD2NK)
This is a safety / feasibility trial evaluating the combination of a humanized anti-GD2 antibody (HU14.18K322A) manufactured at the Children's GMP, LLC at St. Jude with allogeneic natural killer (NK) cells and standard chemotherapy in children with relapsed or refractory neuroblastoma.
Biological: Humanized anti-GD2 antibody
Biological: Natural killer cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Safety/Feasibility Trial of the Addition of the Humanized Anti-GD2 Antibody (hu14.18K322A) With and Without Natural Killer Cells to Chemotherapy in Children and Adolescents With Recurrent/Refractory Neuroblastoma|
- Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2). [ Time Frame: First two courses of treatment (42 days) ] [ Designated as safety issue: Yes ]Unacceptable toxicities are defined as: 1) any grade 4 toxicity that does not return to baseline by day 35, 2) any toxicity requiring the use of pressors, including grade 4 acute capillary leak syndrome or grade 3 or 4 hypotension, 3) any toxicity requiring ventilation support, including grade 4 respiratory toxicity, 4) grade 4 neutropenia or thrombocytopenia lasting > 35 days (only during course 2), and 5) death from toxicity.
- Response to treatment [ Time Frame: Baseline and three (3) weeks following courses 2, 4, and 6 ] [ Designated as safety issue: No ]Clinical outcome measured as response to therapy using the RECIST response evaluation criteria in solid tumors and/or clearing of bone marrow and/or improvement in MIBG scans.
- Time to progression. [ Time Frame: Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years. ] [ Designated as safety issue: No ]
- Event free survival. [ Time Frame: Time from date of study enrollment to date of first event (relapsed or progressive disease, second malignancy or death from any cause) or to the date of last contact for patients without events, assessed up to 4.5 years. ] [ Designated as safety issue: No ]Event-free survival will be estimated using the method of Kaplan and Meier.
- Overall survival [ Time Frame: Time from date of study enrollment to date of death from any cause or to the date of last contact for survivors, assessed up to 4.5 years. ] [ Designated as safety issue: No ]Survival will be estimated using the method of Kaplan and Meier.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells.
Biological: Humanized anti-GD2 antibody
A maximum of 6 courses of therapy may be given on the following schedule:
Other Name: Hu14.18K322A monoclonal antibodyDrug: Chemotherapy
Chemotherapy may include the following at the dosages shown below:
Other Names:Other: Cytokines
Cytokines may be given at the following dosages:
Other Names:Biological: Natural killer cells
NK cells from haploidentical family donor will be infused on day 7 or 8, depending on course. NK cells may be infused in either the inpatient or outpatient setting by a physician, Physician Assistant, Nurse Practitioner, or qualified RN. Careful monitoring and supportive care during NK cell infusion will be guided in part by the Standard Operating Procedures for Lymphocytes Infusions in the St. Jude Nursing Policy & Procedure Manual.
Other Name: NK cells
Eligible participants will receive chemotherapy combined with Hu14.18K322A antibody daily for four consecutive days. Those participants who go on to receive the second course of chemotherapy with Hu14.18K322A will receive an infusion of allogeneic NK cells after the 4th dose of Hu14.18K322A antibody. A maximum of six courses will be given.
- To observe and describe the toxicities associated with humanized anti-GD2 antibody (hu14.18K322A) with and without allogeneic NK cells when given with repeated cycles of chemotherapy to children with refractory/relapsed neuroblastoma.
- To describe response, time to progression, event-free and overall survival.
- To evaluate the feasibility of administering NK cells from a suitable donor after completion of the last dose of hu14.18K322A in three repeated cycles of chemotherapy
Please refer to this study by its ClinicalTrials.gov identifier: NCT01576692
|Contact: Wayne L. Furman, MDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Wayne L. Furman, MD 866-278-5833 email@example.com|
|Principal Investigator: Wayne L. Furman, MD|
|Principal Investigator:||Wayne L. Furman, MD||St. Jude Children's Research Hospital|