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 (GD2NK)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
CURE Childhood Cancer, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01576692
First received: April 10, 2012
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Neuroblastoma
Biological: Humanized anti-GD2 antibody
Drug: Chemotherapy
Other: Cytokines
Biological: Natural killer cells

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2). [ Time Frame: First two courses of treatment (42 days) ] [ Designated as safety issue: Yes ]
    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:
  • Response to treatment [ Time Frame: Baseline and three (3) weeks following courses 2, 4, and 6 ] [ Designated as safety issue: No ]
    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 to progression. [ Time Frame: Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years. ] [ Designated as safety issue: No ]
  • Event free survival. [ 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. ] [ Designated as safety issue: No ]
    Event-free survival will be estimated using the method of Kaplan and Meier.

  • Overall survival [ 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. ] [ Designated as safety issue: No ]
    Survival will be estimated using the method of Kaplan and Meier.


Estimated Enrollment: 20
Study Start Date: April 2012
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells.
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
Other Name: Hu14.18K322A monoclonal antibody
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 Names:
  • Cytoxan
  • Hycamtin
  • Temodar
  • Camptosar
  • Paraplatin
  • Ifex
  • VP-16
  • Vepesid
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
Other Names:
  • IL-2
  • Aldesleukin
  • Proleukin
  • Sargramostim
  • Leukine
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.
Other Name: NK cells

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
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA (Participant):

  • 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).
    • 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.

EXCLUSION CRITERIA (Participant):

  • 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.

INCLUSION CRITERIA (Donor):

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01576692

Contacts
Contact: Wayne L. Furman, MD 866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Wayne L. Furman, MD    866-278-5833    info@stjude.org   
Principal Investigator: Wayne L. Furman, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
CURE Childhood Cancer, Inc.
Investigators
Principal Investigator: Wayne L. Furman, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01576692     History of Changes
Other Study ID Numbers: GD2NK
Study First Received: April 10, 2012
Last Updated: August 18, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
recurrent neuroblastoma
refractory neuroblastoma
natural killer cells

Additional relevant MeSH terms:
Neuroblastoma
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
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014