Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma

• ClinicalTrials.gov Identifier: NCT02502786
• Recruitment Status: Recruiting
• First Posted: July 20, 2015
• Last Update Posted: April 15, 2021
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Children's Hospital Los Angeles; M.D. Anderson Cancer Center; Y-mAbs Therapeutics
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: July 16, 2015
• First Posted Date: July 20, 2015
• Last Update Posted Date: April 15, 2021
• Study Start Date: July 2015
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2015)

event free survival (EFS) [ Time Frame: 12 months ]

EFS is defined as the time from surgery to relapse or death from any cause, recurrence of tumor or second malignancy.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 17, 2015)

time to recurrence [ Time Frame: 12 months ]

Time to recurrence will be estimated using Kaplan-Meier methods. Very few patients are expected to die without relapse (<5%). Recurrence is defined as the radiographic presence of any new lesion that is not attributable to differences in scanning techniques, change in imaging modality or findings thought to represent something other than osteosarcoma, or if a biopsy is performed which shows osteosarcoma.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma
• Official Title: A Phase II Study of Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma
• Brief Summary: The purpose of this study is to find out what effect an antibody called Humanized 3F8 (Hu3F8) and a drug called GM-CSF have on the patient and whether it can keep the patient in remission longer and/or prevent recurrence of the disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent Osteosarcoma

Intervention

• Biological: humanized anti-GD2 antibody
  Other Name: hu3F8
• Drug: GM-CSF

Study Arms

Experimental: humanized anti-GD2 antibody, hu3F8, when combined with GM-CSF

One cycle consists of treatment with hu3F8 at a dose of 2.4mg/kg/dose for 3 days (day 1, 3, and 5) in the presence of subcutaneous (sc) GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. Cycles are repeated at ~2-4 week intervals between first days of hu3F8, through 5 cycles. A maximum of 5 cycles will be administered on protocol.

Interventions:

• Biological: humanized anti-GD2 antibody
• Drug: GM-CSF

• Publications *: Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14. Review.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 12, 2021): 46
• Original Estimated Enrollment (submitted: July 17, 2015): 39
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have recurrent OS. OS must be verified by histopathology review by the site's Department of Pathology. (Patients registered at MSK must have pathology confirmed by MSK Department of Pathology.)
• Patients must be in a ≥2nd complete remission as indicated by appropriate radiologic evaluations at the time of study entry.
• Patients must be ≥ 1 year of age and ≤ to 40 years of age at the time of enrollment.
• Prior therapy: ≥3 weeks should have elapsed since last cytotoxic therapy, immunotherapy or radiation therapy. More than one week should have elapsed since major surgery.

NOTE: Minor surgery (e.g. minor biopsy, central venous catheter placement, shunt revision) is permitted within 1 week prior to enrollment)

• Adequate hematopoietic function defined as:

  • Absolute neutrophil count ≥ 500/ul
  • Absolute lymphocyte count ≥ 500/ul
  • Platelet count ≥ 50,000/ul (transfusion independent)

• Adequate hepatic function as defined by:

  • Total bilirubin of ≤ 1.5 times upper limit of normal (exception is made for patients with Gilbert's syndrome who may be considered eligible if total bilirubin is ≤ 3 times upper limit of normal).
  • AST (SGOT) of ≤ 3 times upper limit of normal
  • ALT (SGPT) of ≤ 3 times upper limit of normal
• Adequate renal function as defined by a serum creatinine of ≤ 1.5 times upper limit of normal
• Adequate cardiac function as defined by a shortening fraction of ≥ 28% or an ejection fraction ≥ 50%
• Adequate pulmonary function as defined by no evidence of dyspnea at rest at no history of exercise intolerance
• Adequate performance status as defined by ECOG score of ≤ 2 or Karnofsky/Lansky score ≥ 50%
• Prior treatment with other anti-GD2 antibodies is allowed (prior treatment with Hu3F8 is NOT allowed), but HAHA antibody titer must be negative
• Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment
• Signed informed consent indicating awareness of the investigational nature of this program

Exclusion Criteria:

• Patients with OS in first complete remission.
• Presence of overt metastatic disease at any site.
• Active life-threatening infection.
• Pregnant women or women who are breast-feeding.
• Inability to comply with protocol requirements.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Months to 40 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Filemon Dela Cruz, MD; 646-888-2275

Contact: Stephen Roberts, MD; 212-639-4034

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02502786
• Other Study ID Numbers: 15-096
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Memorial Sloan Kettering Cancer Center
• Study Sponsor: Memorial Sloan Kettering Cancer Center

Collaborators

• Children's Hospital Los Angeles
• M.D. Anderson Cancer Center
• Y-mAbs Therapeutics

Investigators

• Principal Investigator: Filemon Dela Cruz, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: April 2021