Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma
Condition: Recurrent Osteosarcoma
MeSH terms: Osteosarcoma; Recurrence
Intervention: Glembatumumab Vedotin; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: Glembatumumab vedotin; Immunoconjugates; Immunotoxins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 12 Years
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well glembatumumab vedotin works in treating patients with
      osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory).
      Monoclonal antibodies, such as glembatumumab vedotin, may find tumor cells and help kill
      them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have had histologic verification of osteosarcoma at original diagnosis
             or relapse

          -  Patients must have measurable disease according to RECIST 1.1, and have relapsed or
             become refractory to conventional therapy

          -  Patient must have archival 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 chemotherapy: must not have received within 2 weeks of entry
                  onto this study (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 RT (small port); >= 6
                  months 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

               -  Monoclonal antibodies: must not have received any monoclonal based therapies
                  within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth
                  factor given to control the cancer) within 2 weeks, prior to study enrollment

          -  Peripheral absolute neutrophil count (ANC) >= 1000/uL

          -  Platelet count >= 75,000/uL (transfusion independent)

          -  Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

          -  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:

               -  Age 1 to < 2 years (male and female: 0.6 mg/dL)

               -  Age 2 to < 6 years (male and female: 0.8 mg/dL)

               -  Age 6 to < 10 years (male and female: 1 mg/dL)

               -  Age 10 to < 13 years (male and female: 1.2 mg/dL)

               -  Age 13 to < 16 years (male: 1.5 mg/dL and female: 1.4 mg/dL)

               -  Age >= 16 (male: 1.7 mg/dL and female: 1.4 mg/dL)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 110
             U/L; for the purposes of this study the ULN for SGPT is defined as 45 U/L

          -  Serum albumin > 2 g/dL

          -  Shortening fraction of >= 27% by echocardiogram, or

          -  Ejection fraction of >= 50% by radionuclide angiogram

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met

        Exclusion Criteria:

          -  Patients with > grade 2 neuropathy according to the Modified ("Balis") Pediatric Scale
             of Peripheral Neuropathies will be excluded except in cases in which neuropathy is
             secondary to prior surgery

          -  Patients who have previously received CDX-011 (CR011-vc monomethyl auristatin E
             [MMAE]; CDX-011) or other MMAE-containing agents

          -  Patients who have received other investigational drugs within 2 weeks or 5 half-lives
             (whichever is longer) prior to study enrollment

          -  Patients with a history of allergic reactions attributed to compounds of similar
             composition to dolastatin or auristatin; compounds of similar composition include
             auristatin PHE as an anti-fungal agent, auristatin PE (TZT-1027, Soblidotin,
             NSC-654663) as an anti-tumor agent and symplostatin 1 as an anti-tumor agent

          -  Patients with known central nervous system metastasis are not eligible

          -  Patients who have had major surgery within 2 weeks prior to enrollment are not
             eligible; procedures such as placement of a central vascular catheter, or limited
             tumor biopsy, are not considered major surgery

          -  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 and for 2 months after the end of study treatment