A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma
Primary Purpose
Neuroblastoma, Melanoma, Osteosarcoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anti-GD2 antibody
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma
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 (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.
- 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.
Sites / Locations
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Group 1
Arm Description
Participants who consent to the study will receive Anti-GD2 antibody.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT00743496
First Posted
August 27, 2008
Last Updated
August 14, 2017
Sponsor
St. Jude Children's Research Hospital
Collaborators
Evan T.J. Dunbar Neuroblastoma Foundation, Duke University, University of Wisconsin, Madison, University Children's Hospital Tuebingen, Children's Hospital Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT00743496
Brief Title
A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma
Official Title
A Phase I Trial Of The Humanized Anti-GD2 Antibody (HU14.18K322A) In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
October 8, 2008 (Actual)
Primary Completion Date
April 1, 2014 (Actual)
Study Completion Date
April 18, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Evan T.J. Dunbar Neuroblastoma Foundation, Duke University, University of Wisconsin, Madison, University Children's Hospital Tuebingen, Children's Hospital Los Angeles
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
SJGD2 is a Phase I dose finding study. The primary purpose of this phase I study is to determine the 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).
Initially, in Part A, one research participant will be treated at the lowest dose level of hu14.18K322A antibody [2 mg/m^2 daily for 4 consecutive days every 28 days (1 course)], and if no toxicity is observed then the next participant will be treated at the next dose level. This is continued until the first instance of biological activity (in the form of grade 2 side effects) is observed and from that point on a traditional phase I study design will be followed. A maximum of 4 courses may be given.
Part B: Hu14.18K322A antibody will be administered intravenously (IV) at a starting dose of 50 mg/m^2/dose weekly for 4 doses per course. One course is considered 28 days. A maximum of 8 courses may be given.
Part C: Hu14.18K322A antibody will be administered to 6 patients each with refractory/recurrent osteosarcoma at a maximum tolerated dose (MTD) of 60 mg/m^2 daily for 4 consecutive days every 28 days (Part C1). A cohort of patients with refractory/recurrent osteosarcoma or Ewing sarcoma will also be administered hu14.18K322A antibody at starting dose of 40 mg/m^2/dose weekly for 4 doses per course (Part C2). Participants will continue on treatment for a maximum of 8 courses.
Secondary objectives include:
Estimate the response rate, within the confines of a phase I study, to the humanized anti-GD2 antibody, hu14.18K322A.
Evaluate the pharmacokinetics of hu14.18K322A.
Examine whether or not human anti-human antibodies (HAHA) develop in participants receiving hu14.18K322A.
Assess the tolerability of the hu14.18K322A at the MTD of the daily x4 and the weekly dosing in patients with refractory or recurrent osteosarcoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Melanoma, Osteosarcoma, Ewing Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Participants who consent to the study will receive Anti-GD2 antibody.
Intervention Type
Biological
Intervention Name(s)
Anti-GD2 antibody
Intervention Description
Anti-GD2 antibody
Primary Outcome Measure Information:
Title
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.
Time Frame
within 12 months of the start of therapy
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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 (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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Bishop, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32169872
Citation
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. Erratum In: J Immunother Cancer. 2020 Jun;8(1):
Results Reference
derived
PubMed Identifier
24711551
Citation
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.
Results Reference
derived
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude
Learn more about this trial
A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma
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