A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma

NCT00743496 | Completed Phase 1 FDA Drug

• 3 other identifiers: SJGD2ED FDNNCI-2011-01150
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Relapsed and/or refractory neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma are considered difficult to treat and cure. For this 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. Two schedules of hu14.18K322A antibody will be evaluated in this study, (1) daily for four consecutive days schedule every 28 days and (2) 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 one or more of the criteria for off-treatment are met.

Conditions

Neuroblastoma; Melanoma; Osteosarcoma; Ewing Sarcoma

Outcome Measures

Primary Outcomes (1)

• Determine maximum tolerated dose and dose-limiting toxicity of the humanized monoclonal anti-GD2 antibody, hu14.18K322A, in research participants with neuroblastoma, osteosarcoma, Ewing sarcoma and melanoma.

  within 12 months of the start of therapy

Study Arms (1)

Group 1

EXPERIMENTAL

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

Biological: Anti-GD2 antibody

Interventions

Anti-GD2 antibody BIOLOGICAL

Anti-GD2 antibody

Group 1

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:
• 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 (i.e. participants are eligible until they reach their 22nd birthday).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Evan T.J. Dunbar Neuroblastoma Foundation: collaborator
• Duke University: collaborator
• University of Wisconsin, Madison: collaborator
• University Children's Hospital Tuebingen: collaborator
• Children's Hospital Los Angeles: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (2)

• Goldberg JL, Navid F, Hank JA, Erbe AK, Santana V, Gan J, de Bie F, Javaid AM, Hoefges A, Merdler M, Carmichael L, Kim K, Bishop MW, Meager MM, Gillies SD, Pandey JP, Sondel PM. Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma. J Immunother Cancer. 2020 Mar;8(1):e000590. doi: 10.1136/jitc-2020-000590.

  PMID: 32169872 DERIVED

• Navid F, Sondel PM, Barfield R, Shulkin BL, Kaufman RA, Allay JA, Gan J, Hutson P, Seo S, Kim K, Goldberg J, Hank JA, Billups CA, Wu J, Furman WL, McGregor LM, Otto M, Gillies SD, Handgretinger R, Santana VM. Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J Clin Oncol. 2014 May 10;32(14):1445-52. doi: 10.1200/JCO.2013.50.4423. Epub 2014 Apr 7.

  PMID: 24711551 DERIVED

Related Links

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

MeSH Terms

Conditions

Neuroblastoma; Melanoma; Osteosarcoma; Sarcoma, Ewing

Interventions

humanized 3F8 anti-GD2 monoclonal antibody

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; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Study Officials

• Michael Bishop, 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: August 27, 2008
• First Posted: August 28, 2008
• Study Start: October 8, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 18, 2014
• Last Updated: August 17, 2017

Record last verified: 2017-08

Locations

US (1)