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

NCT01576692 | Completed Phase 1 FDA Drug FDA Device

• 2 other identifiers: GD2NKNCI-2012-00495
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma; refractory neuroblastoma; natural killer cells

Outcome Measures

Primary Outcomes (1)

• 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.

  First two courses of treatment (42 days)

Secondary Outcomes (4)

• Response to treatment

  Baseline and three (3) weeks following courses 2, 4, and 6

• Time to progression.

  Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years.

• 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.

• 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.

Study Arms (1)

Treatment

EXPERIMENTAL

Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System.

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

Interventions

Humanized anti-GD2 antibody BIOLOGICAL

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

Also known as: Hu14.18K322A monoclonal antibody

Treatment

Chemotherapy DRUG

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

Also known as: Cytoxan, Hycamtin, Temodar, Camptosar, Paraplatin, Ifex, VP-16, Vepesid

Treatment

Cytokines OTHER

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

Also known as: IL-2, Aldesleukin, Proleukin, Sargramostim, Leukine

Treatment

Natural killer cells BIOLOGICAL

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.

Also known as: NK cells

Treatment

CliniMACS DEVICE

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.

Also known as: Cell Selection System

Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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) disease.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• CURE Childhood Cancer, Inc.: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Neuroblastoma

Interventions

humanized 3F8 anti-GD2 monoclonal antibody; Hu14.18K322A monoclonal antibody; Drug Therapy; Cyclophosphamide; Topotecan; Temozolomide; Irinotecan; Carboplatin; Ifosfamide; Etoposide; Cytokines; Interleukin-2; aldesleukin; sargramostim; IL32 protein, human

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Oxazines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Lymphokines

Study Officials

• Wayne L. Furman, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2012
• First Posted: April 12, 2012
• Study Start: April 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 17, 2018
• Last Updated: November 15, 2018

Record last verified: 2018-11

Locations

US (1)