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.
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. Primary Objective: * 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. Secondary Objective: * 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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
A maximum of 6 courses of therapy may be given on the following schedule: * Courses 1, 3, and 5: Humanized anti-GD2 antibody + chemotherapy * Courses 2, 4, and 6: Humanized anti-GD2 antibody + chemotherapy, with or without natural killer (NK) cells (depending on availability of appropriate NK donor) * Humanized anti-GD2 antibody (hu14.18 K322A) dosage: 40 mg/m\^2)/dose, over 4 hours daily * NK Cell dosage: minimum of 0.1 \* 10\^6 cells/kg; maximum of 400 \* 10\^6 CD45+ cells/kg, given once
Chemotherapy may include the following at the dosages shown below: * cyclophosphamide: 400 mg/m\^2 IV days 1-5 * topotecan: 1.2 mg/m\^2 IV days 1-5 * temozolomide: 150 mg/m\^2 PO at least 1 hour before irinotecan * irinotecan: 50 mg/m\^2 IV over 1 hour daily for 5 days * carboplatin (AUC 8-dosing based on GFR), IV day 1 only * ifosfamide: 2 g/m2 IV days 1-3 * etoposide: 100 mg/m2 days 1-3
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2).
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.
Time frame: First two courses of treatment (42 days)
Response to treatment
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 frame: Baseline and three (3) weeks following courses 2, 4, and 6
Time to progression.
Time frame: Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years.
Event free survival.
Event-free survival will be estimated using the method of Kaplan and Meier.
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.
Overall survival
Survival will be estimated using the method of Kaplan and Meier.
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.
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Cytokines may be given at the following dosages: * interleukin-2: 1 million units/m\^2 SQ beginning day 6 of each chemotherapy course and continued every other day for 6 doses * GM-CSF: 250 mcg/m\^2/day beginning on day 7 or day 8 of chemotherapy course and continued daily through the nadir until ANC \>2,000/mm\^3
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.
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.