Disseminated Neuroblastoma, Recurrent Neuroblastoma
Conditions
Keywords
Neuroblastoma, Solid tumor, Immunotherapy targeting GD2, Bispecific antibodies, Activated T cells
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALIL-2
Given SC
BIOLOGICALGD2Bi-aATC
Given IV
BIOLOGICALGM-CSF
Given SC
OTHERlaboratory evaluations of immune responses
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Virginia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Months to 29 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of GD2Bi-aATC | 35 days | Safety of GD2Bi-aATC infusions is evaluated to determine MTD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor activity | Up to 12 months | Objective response rate to GD2Bi-aATC infusions |
| Immune responses after GD2Bi-aATC infusions | Up to 12 months | In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes |
Countries
United States
Contacts
Primary ContactHolly Davis
Outcome results
None listed