SJGD2: Monoclonal Antibody Therapy in Treating Younger Patients with Relapsed or Refractory Neuroblastoma, Osteosarcoma, or Melanoma

A Phase I Trial of the Humanized Anti-GD2 Antibody(HU14.18K322A) in Children and Adolescents with Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma

Categories:

Solid Tumor

Phase I/II

Diseases Treated:

Neuroblastoma, osteosarcoma, melanoma or Ewing sarcoma

Eligibility Overview:

  • Up to 21 years of age
  • Diagnosis of neuroblastoma, melanoma, osteosarcoma  or Ewing sarcoma that has come back or did not respond to previous treatment
  • Any uncontrolled infection
  1. Brief Summary

    Relapsed and/or refractory neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma are considered difficult to treat and cure. SJGD2 is a phase 1 dose finding study. We are testing the use of a new experimental (investigational) antibody called hu14.18K322A. GD2 is expressed on the surface of most of these tumor types.

    Primary Objective

    To determine maximum tolerated dose (MTD) and dose-limiting toxicity of the humanized monoclonal anti-GD2 antibody, hu14.18K322A, in research participants with refractory or relapsed neuroblastoma or melanoma (Parts A and B) or osteosarcoma or Ewing sarcoma (Part C).

    Trial Outline

    • Two schedules of hu14.18K322A antibody will be evaluated in this study
      • Daily for 4 consecutive days schedule every 28 days and
      • Once weekly for 4 weeks schedule every 28 days
    • Approximately 25-40 participants will be required to define the maximum tolerated dose for each schedule
    • Participants will continue on treatment for a maximum of 4 to 8 courses or until 1 or more of the criteria for off-treatment are met

    Intervention

    Biological: Anti-G2 antibody

    Study Arms

    Experimental: Group 1

    Participants who consent to the study will receive anti-GD2 antibody.

    Eligibility Criteria

    Inclusion Criteria:

    • Diagnosis
      • Part A: Recurrent or refractory neuroblastoma or melanoma
      • Part B: Recurrent or refractory neuroblastoma or melanoma
      • Part C: Recurrent or refractory osteosarcoma and Ewing sarcoma
    • Age: ≤ 21 years of age at the time of enrollment
    • Does not have a clinically significant neurologic deficit or objective peripheral neuropathy (greater than or equal to grade 2). Peripheral (sensory or motor) neuropathy related to limb sparing procedure or amputation is allowed.
    • Life expectancy: at least 8 weeks.
    • Organ Function: Must have adequate organ and marrow function
    • Performance status: Karnofsky ≥ 50 for > 10 years of age; Lansky ≥ 50 for children < 10 years of age.
    • Prior Therapy: Patient 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. 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 14 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.
    • Patients 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:

    • Prior monoclonal antibody: Participants having received in vivo monoclonal antibodies for biologic therapy or for tumor imaging are eligible provided they did not experience a severe allergic reaction with the antibody.
    • 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

    Study Design

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

     

  2. About this clinical trial

    SJGD2 is a Phase I clinical trial for children, adolescents and young adults with neuroblastoma, melanoma, osteosarcoma or Ewing sarcoma. These cancers are all solid tumor cancers, which means they are formed by an abnormal growth of cells and tissue, creating a lump or solid mass.

    Neuroblastoma, melanoma, osteosarcoma or Ewing sarcoma that has come back or did not respond to previous treatment can be difficult to treat. More effective treatment options are needed, which is why St. Jude is offering this clinical trial.

    Purpose of this clinical trial

    In this clinical trial, the main goal is to find out if an investigational “humanized” monoclonal antibody called hu14.18K322A is safe to give to children, adolescents and young adults with neuroblastoma, melanoma, osteosarcoma and Ewing sarcoma.

    Antibodies are part of the body’s normal immune (defense) system that look for and attack certain cells that it sees as “different” and harmful.  Examples of “different” and harmful cells include bacteria, viruses and cancer cells.

    The hu14.18K322A antibody is a man-made version of an immune system protein that finds and attaches to the surface of most neuroblastoma, melanoma, osteosarcoma and Ewing sarcoma cells. It is hoped that the hu14.18K322A antibody, together with the body’s immune system, will attack and kill the cancer cells without destroying nearby healthy cells.

    Treatment

    In this trial, all participants will receive treatment with hu14.18K322A on one of the following regimens:

    • Once a day – for  four days in a row (repeated every 28 days for a maximum of  eight courses)
    • Once a week – for  four weeks (repeated every 4 weeks for a maximum of  eight courses)

    Eligibility overview

    • Up to 21 years of age
    • Diagnosis of neuroblastoma, melanoma, osteosarcoma  or Ewing sarcoma that has come back or did not respond to previous treatment
    • Any uncontrolled infection
  3. SJGD2  Quick View
    Sponsor St. Jude Children's Research Hospital
    Collaborators
    • Evan T. J. Dunbar Neuroblastoma Foundation, Inc
    • Duke University
    • University of Wisconsin, Madison
    • University Children’s Hospital Tuebingen
    • Children's Hospital Los Angeles
    Clinicaltrials.gov identifier NCT00743496
    Trial start date August 2008
    Estimated enrollment 75
    Study type  Interventional
    Study phase Phase 1
    Conditions
    • Neuroblastoma
    • Melanoma
    • Osteosarcoma
    • Ewing sarcoma
    Ages Up to 21 years
    Principal investigator Michael Bishop, MD
    Study site St. Jude Children's Research Hospital
    For a consultation or to discuss SJGD2 St. Jude Physician/Patient Referral Office
    1-888-226-434
    referralinfo@stjude.org

Contact

Michael Bishop, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

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