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

Phase 1

Completed

• Conditions: Neuroblastoma
• Interventions: Biological: Humanized anti-GD2 antibody; Drug: Chemotherapy; Other: Cytokines; Biological: Natural killer cells; Device: CliniMACS

• Registration Number: NCT01576692
• Lead Sponsor: St. Jude Children's Research Hospital

Brief 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

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-04-10
• Study First Submitted QC: 2012-04-11
• Study First Posted: 2012-04-12
• Primary Completion: 2014-10
• Study Completion: 2018-10-17
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-14
• Last Update Posted: 2018-11-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	CliniMACS	Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.
Treatment	Humanized anti-GD2 antibody	Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.
Treatment	Chemotherapy	Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.
Treatment	Cytokines	Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.
Treatment	Natural killer cells	Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.

Primary Outcome Measures

Name	Time	Method
Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2).	First two courses of treatment (42 days)	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.

Secondary Outcome Measures

Name	Time	Method
Time to progression.	Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years.
Response to treatment	Baseline and three (3) weeks following courses 2, 4, and 6	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.
Event free survival.	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.	Event-free survival will be estimated using the method of Kaplan and Meier.
Overall survival	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.	Survival will be estimated using the method of Kaplan and Meier.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States