NCT01576692

Combination Chemotherapy, Monoclonal Antibody, and Natural Killer Cells in Treating Young Patients With Recurrent or Refractory Neuroblastoma

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Humanized anti-GD2 antibody	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
DRUG	Chemotherapy	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
OTHER	Cytokines	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
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.
DEVICE	CliniMACS	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.

Timeline

• Start date: 2012-04-01
• Primary completion: 2014-10-01
• Completion: 2018-10-17
• First posted: 2012-04-12
• Last updated: 2018-11-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study