This phase II trial studies how well dinutuximab works when given with sargramostim in
treating patients with osteosarcoma that has come back after treatment (recurrent).
Dinutuximab is a type of drug called a monoclonal antibody. It is designed to recognize a
specific target on the surface of cancer cells. It then attaches to the cancer cells and
kills them, without harming normal cells. Sargramostim may help the body increase the amount
of of white blood cells it produces, which help the body fight off infections. Giving
sargramostim with dinutuximab may help the dinutuximab work better and kill more cancer
cells.
Minimum age: N/A.
Maximum age: 29 Years.
Gender(s): Both.
Inclusion Criteria:
- Patients must have histologic diagnosis of osteosarcoma at original diagnosis
- Patients must have had at least one episode of disease recurrence in the lungs
without limitation on number of episodes of recurrence as long as they meet the
following criteria:
- Surgical resection of all possible sites of suspected pulmonary metastases in
order to achieve a complete remission within 4 weeks prior to study enrollment**
- Pathologic confirmation of metastases from at least one of the resected sites
- For patients with bilateral pulmonary metastases, resection must be
performed from both lungs and the study enrollment must be within 4 weeks
from date of the last lung surgery
- Note: post-operative radiographic confirmation of complete remission will not be
required as long as the operating surgeon believes that all sites of disease
were resected; patients with positive microscopic margins will be eligible to
enroll
- Patient must have adequate tumor specimen available for submission
- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive anti-cancer therapy: must not have been received within 2 weeks
of study entry (4 weeks if prior nitrosourea)
- Biologic (anti-neoplastic agent): at least 7 days since the completion of
therapy with a biologic agent
- Radiation therapy (RT): >= 2 weeks for local palliative radiation therapy (RT)
(small port); >= 6 weeks must have elapsed if prior craniospinal RT or if >= 50%
radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone
marrow (BM) radiation
- Surgery: >= 2 weeks from last major surgery, with the exclusion of a central
line placement and core needle or small open biopsies
- Patient must not have received pegfilgrastim (Neulasta) within 14 days of enrollment
- Patient must not have received filgrastim (G-CSF, Neupogen) within 7 days of
enrollment
- Patient must not have received immune suppressants: corticosteroids (for other than
allergic reactions and anaphylaxis), cyclosporine or tacrolimus within 7 days of
enrollment
- Note: the use of topical and/or inhalational steroids is allowed
- Total absolute phagocyte count (APC = [%neutrophils + %monocytes) x white blood cells
[WBC]) is at least 1000/uL
- Platelet count >= 50,000/uL
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1. 73 m^2 or
- A serum creatinine based on age/gender as follows:
- 1 month to < 6 months: 0. 4 (male) 0. 4 (female)
- 6 months to < 1 year: 0. 5 (male), 0. 5 (female)
- 1 to < 2 years: 0. 6 (male), 0. 6 (female)
- 2 to < 6 years: 0. 8 (male), 0. 8 (female)
- 6 to < 10 years: 1 (male), 1 (female)
- 10 to < 13 years: 1. 2 (male), 1. 2 (female)
- 13 to < 16 years: 1. 5 (male), 1. 4 (female)
- >= 16 years: 1. 7 (male), 1. 4 (female)
- Total bilirubin =< 1. 5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
- Serum albumin >= 2 g/dL
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
- No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse
oximetry > 94%
- Patients with a known seizure disorder may be enrolled if on anticonvulsants and/or
well controlled
- Central nervous system (CNS) toxicity including peripheral neuropathy =< grade 2
Exclusion Criteria:
- Patients with distant bone metastases at original diagnosis or relapse (patients with
only skip lesions will be eligible)
- Patients with concurrent local and pulmonary recurrence at the time of enrollment;
note: patients who had local recurrence previously that has been treated and now
present with an isolated pulmonary recurrence and meet the surgical resection
criteria stated above will be eligible
- Patients with primary refractory disease with progression of the primary tumor on
initial therapy
- Patients with CNS disease involvement at the time of most recent episode of disease
recurrence preceding enrollment
- Patients with a prior hypersensitivity reaction to sargramostim
- Patients who have received prior anti-GD2 therapy, including chimeric antigen
receptor (CAR) T cells directed against GD2 antigen
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their
infants
- Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation