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 January 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01576692
First received: April 10, 2012
Last updated: January 10, 2014
Last verified: January 2014

April 10, 2012
January 10, 2014
April 2012
October 2014   (final data collection date for primary 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). [ 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.
Same as current
Complete list of historical versions of study NCT01576692 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
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
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

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.

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
Interventional
Not Provided
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neuroblastoma
  • 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
Experimental: Treatment
Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells.
Interventions:
  • Biological: Humanized anti-GD2 antibody
  • Drug: Chemotherapy
  • Other: Cytokines
  • Biological: Natural killer cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
April 2018
October 2014   (final data collection date for primary outcome measure)

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.
Both
up to 21 Years
No
Contact: Wayne L. Furman, MD 866-278-5833 info@stjude.org
United States
 
NCT01576692
GD2NK
No
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Not Provided
Principal Investigator: Wayne L. Furman, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP