activated t cells armed with gd2 bispecific antibody in children and young adults with neuroblastoma and osteosarcoma

Conditions: Disseminated Neuroblastoma; Recurrent Neuroblastoma

Summary: previous research has demonstrated that investigators can coat (arm) t cells with a special molecule called gd2 bispecific antibody that will help t cells recognize neuroblastoma and osteosarcoma cells and kill them. this bispecific antibody recognizes gd2, a protein found on almost all neuroblastoma and osteosarcoma cells. the investigators put the gd2 bispecific antibody on t cells and give large numbers of these t cells back to patients. the investigators think that these t cells may have a better chance of killing gd2 expressing tumor cells when they are armed with gd2 bispecific antibody. this trial studies the side effects and best dose of activated t cells armed with gd2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other gd2-positive solid tumors.

primary objectives: i. to perform a phase i dose-escalation study in patients with recurrent or refractory neuroblastoma (nb) and other gd2-positive tumors to evaluate the safety and tolerability and to determine the maximum tolerated dose (mtd) for anti-cd3 x hu3f8 bispecific antibody (gd2bi)-armed activated t cells (aatc) infused twice a week for a total of eight infusions in combination with daily il-2 (300,000 iu/m\^2/day) and gm-csf (250 ug/m\^2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10\^6 cells/kg/infusion dose levels. ii. to conduct a phase ii clinical trial to explore efficacy and confirm the toxicity profile of gd2bi-aatc combined with il-2 and gm-csf in a phase ii expansion cohort of 22 patients with neuroblastoma (nb) using mtd determined in the phase i. secondary objectives: i. evaluate immune responses in the phase i/ii trial by sequential monitoring of anti-nb cytotoxicity of peripheral blood lymphocytes and ifn-gamma elispots directed at nb lines. ii. to evaluate persistence of aatc in the blood and tumor biopsies by staining for murine igg2a to confirm trafficking of armed t cells to tumor. iii. to conduct exploratory study of (18f fdg) positron emission tomography (pet)/computed tomography (ct) after armed atc infusions in selected patients with pet/ct measurable soft tissue and skeletal lesions. outline: this is a phase i, dose-escalation study of okt3/humanized 3f8 bispecific antibody-aatc followed by a phase ii study. patients receive il-2 subcutaneously (sc) daily on days -2 to 35, sargramostim sc twice weekly for 4 weeks, and okt3/humanized 3f8 bispecific antibody-aatc intravenously (iv) over 30 minutes twice weekly for 4 weeks. after completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.

Eligibility criteria:
the study is now in the phase ii expansion phase. inclusion criteria for phase ii: * the target tumor is limited to neuroblastoma and the diagnosis should be histologically verified. * patients must have refractory or recurrent malignancy; patient's current disease state must be one for which no known curative therapy is available; * patients should not receive any other experimental or phase 1 therapy within 3 weeks prior to study enrollment and monoclonal antibody therapy within 6 weeks * to be eligible for phase i study patients should have primary refractory or relapsed disease as evidenced by: * local tumor recurrence measurable on ct or magnetic resonance imaging (mri) scans with or without metastatic lesions * refractory bone marrow involvement in patients with nb * nb with mibg-positive skeletal lesions * the presence of radiographically measurable disease immediately prior to start of phase i immunotherapy is not an eligibility requirement in the following situations: * in patients with nb who have documented bone marrow (bm) involvement; * in patients with nb who have mibg-positive bony lesion(s); * an additional eligibility requirement for phase ii study includes the presence of radiographically measurable disease with the exception of mibg-positive nb or nb with bone marrow involvement: * patients must have a lansky or karnofsky performance status score of \>= 70 * patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy * myelosuppressive chemotherapy: must not have received within 3 weeks of starting immunotherapy (it) * hematopoietic growth factors: at least 7 days since the last dose of growth factor therapy * immunotherapy: at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody * normal organ function * all patients or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines * all institutional, food and drug administration (fda), and national cancer institute (nci) requirements for human studies must be met exclusion criteria: * patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are postmenarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 3 months after the last dose of gd2bi-aatc; breastfeeding women should be excluded * patients who have an uncontrolled infection are not eligible * patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Keywords: neuroblastoma solid tumor immunotherapy targeting gd2 bispecific antibodies activated t cells