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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02502786

Collaborator

Children's Hospital Los Angeles (Other), M.D. Anderson Cancer Center (Other), Y-mAbs Therapeutics (Industry)

Enrollment

Locations

Arm

Duration (Months)

15.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Osteosarcoma	Biological: humanized anti-GD2 antibody Drug: GM-CSF	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: humanized anti-GD2 antibody Other Names: hu3F8 Drug: GM-CSF

Arm

Intervention/Treatment

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.

Biological: humanized anti-GD2 antibody

Other Names:

hu3F8

Drug: GM-CSF

Outcome Measures

Primary Outcome Measures

event free survival (EFS) [12 months]
EFS is defined as the time from surgery to relapse or death from any cause, recurrence of tumor or second malignancy.

Secondary Outcome Measures

time to recurrence [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Months to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles (Data Collection Only)	Los Angeles	California	United States	90027
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	MD ANDERSON CANCER CENTER (Data Collection Only)	Houston	Texas	United States	77030