Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
The investigators have found in the previous research that the 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 neuroblastoma 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.
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
|Eligible Ages||13 Months - 29 Years|
Inclusion Criteria:- The target tumor is limited to neuroblastoma, osteosarcoma, and GD2-positive solid tumors; patients must have histologic verification of neuroblastoma, osteosarcoma or other GD2-positive solid malignancy including desmoplastic small round cell tumor (DSRCT) at original diagnosis or time of recurrence - Tumor GD2 status does not need to be determined for eligibility of the patients with neuroblastoma, osteosarcoma or DSRCT; - 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 - lung lesions consistent with metastatic osteosarcoma (OST) - 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); - In patients with OST who had resection of the pulmonary 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
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 0: Exploratory study involving very limited human exposure to the drug to determine whether a drug is modulating its target.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
|Phase 1/Phase 2|
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Barbara Ann Karmanos Cancer Institute|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Desmoplastic Small Round Cell Tumor, Disseminated Neuroblastoma, Metastatic Osteosarcoma, Recurrent Neuroblastoma, Recurrent Osteosarcoma|
- 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.
- 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.
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Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Shakeel Modak, M.D.