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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

21 Years
Open (Enrolling)

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Trial Information

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

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

Inclusion Criteria


- Diagnosis of recurrent or refractory neuroblastoma.

- Age < 22 years at the time of enrollment.

- Measurable or evaluable (detectable by bone scan or MIBG, but not measurable)

- Organ function: Must have adequate organ and marrow function as defined by the
following parameters:

- Bone marrow: Absolute neutrophil count (ANC) > 750/mm3; Platelets > 75,000/mm3
(no platelet transfusions for at least 1 week)

- Hepatic: Total bilirubin ≤ 2 x upper limit of normal (ULN) for age; SGPT (ALT) ≤
2.5 x ULN for age.

- Renal: Creatinine clearance or radioisotope GFR equal to or >70 ml/min/1.73m2
OR serum creatinine based on age as follows:

- Age 5 years of age and under, then maximum serum creatinine 0.8 mg/dL

- Age >5 and equal to or <10 years, then maximum serum creatinine 1.0 mg/dL

- Age >10 and equal to or <15 years, then maximum serum creatinine 1.2 mg/dL

- Age >15 years, then maximum serum creatinine 1.5 mg/dL

- Cardiovascular: Shortening fraction > or equal to 27% by echocardiogram;
Corrected QT interval < or equal to 450 milliseconds

- Performance status: Karnofsky > or equal to 50 for > 10 years of age; Lansky > or
equal to 50 for children equal to or < 10 years of age.

- Prior therapy: Participant must have fully recovered from the acute toxic effects of
all prior therapy prior to enrolling on study.

- Myelosuppressive chemotherapy: Must not have received myelosuppressive therapy
within 2 weeks prior to study entry (4 weeks if nitrosurea).

- Biologic (anti-neoplastic agent): At least 7 days since the completion of
therapy with biologic agent, including retinoic acid. At least 6 weeks must
have elapsed since prior therapy that includes a monoclonal antibody.
Participants receiving IVIG are eligible; however, participant must not receive
IVIG during the 4 days of antibody infusion.

- Radiation therapy: At least 2 weeks since prior local radiation therapy at the
time of study entry.

- Growth factors: Must not have received hematopoietic growth factors (G-CSF,
GM-CSF) for at least 1 week prior to study entry.

- Investigational agent: Must not have received investigational agent within 7
days of study entry.

- Immune therapy: Must not have received immunosuppressive (including
glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2
weeks of study entry. Steroid containing inhalers, steroid replacement for
adrenal insufficiency and steroid premedication for prevention of transfusion or
imaging contrast-agent related allergic reaction will be permitted.

- Participants may have had prior CNS metastasis providing: CNS disease has been
previously treated and CNS disease has been clinically stable for 4 weeks prior to
study entry (assessment must be made by CT or MRI).

- Written informed consent following institutional and federal guidelines.


- Prior monoclonal antibody: Participants having received in vivo monoclonal anti-GD2
antibodies for biologic therapy or for tumor imaging are ineligible if they have
experienced a severe allergic reaction while receiving prior anti-GD2 therapy.

- Pregnancy or breast feeding: Study participants who are pregnant are not eligible
for this study. Pregnancy tests must be obtained in girls who are > 10 years of age
or post-menarchal within 7 days prior to study enrollment. Males or females of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method during participation in the trial. Breast feeding
should be discontinued if a mother wishes to participate in this study.

- Allergy: Known hypersensitivity to other recombinant human antibodies.

- An uncontrolled infection.

- Participants who have not started protocol therapy within 7 days of study enrollment.


- Donor is a partially matched family member.

- Donor is HIV negative.

- Donor is at least 18 years of age.

- Donor is not pregnant.

- Donor does not have any other medical condition that, in the opinion of an
independent physician, precludes performance of an apheresis procedure.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2).

Outcome Description:

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.

Outcome Time Frame:

First two courses of treatment (42 days)

Safety Issue:


Principal Investigator

Wayne L. Furman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Jude Children's Research Hospital


United States: Institutional Review Board

Study ID:




Start Date:

April 2012

Completion Date:

April 2018

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • refractory neuroblastoma
  • natural killer cells
  • Neuroblastoma



St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794