Disseminated NeuroblastomaPhase 1/2NCT02173093
Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma
A Phase 1/2 study testing IL-2, GD2Bi-aATC and GM-CSF in people with Disseminated Neuroblastoma and Recurrent Neuroblastoma, run by University of Virginia at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 months to 29 years
- Conditions the study is for
- Disseminated Neuroblastoma, Recurrent Neuroblastoma
- What is being tested?
- IL-2, GD2Bi-aATC and GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2014to Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 months to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 19Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Holly Davis contact
United States3 sites, 3 recruiting
- Recruiting
University of Virginia, Department of Pediatrics, Hematology/Oncology
Charlottesville, Virginia, 22908
Daniel (Trey) Lee, MD, 434-297-4289, DWL4Q@Virginia.edu
Daniel (Trey) Lee, MD
- Recruiting
Children's Hospital of Michigan
Detroit, Michigan, 48201
Maxim Y. Yankelevich, MD, 313-745-5516, myankele@med.wayne.edu
Diana Gomez, MPH, 313-745-7163
- Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Shakeel Modak, M.D., modaks@mskcc.org
Shakeel Modak, M.D.
About this study
Official title: Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- IL-2, GD2Bi-aATC, GM-CSF, laboratory evaluations of immune responses
- Keywords
- Neuroblastoma, Solid tumor, Immunotherapy targeting GD2, Bispecific antibodies, Activated T cells
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2Biological
Also called aldesleukin, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Given SC
GD2Bi-aATCBiological
Also called GD2Bi-armed aATC
Given IV
GM-CSFBiological
Also called sargramostin, Leukine, Prokine
Given SC
laboratory evaluations of immune responsesOther
Also called laboratory biomarker analysis
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (IL-2, GM-CSF, GD2Bi-aATC) | Experimental | Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy. Receives: Biological: IL-2; Biological: GD2Bi-aATC; Biological: GM-CSF; Other: laboratory evaluations of immune responses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of GD2Bi-aATC
Safety of GD2Bi-aATC infusions is evaluated to determine MTD
Measured: 35 days
Secondary outcomes (2)
Anti-tumor activity
Objective response rate to GD2Bi-aATC infusions
Measured: Up to 12 months
Immune responses after GD2Bi-aATC infusions
In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Disseminated NeuroblastomaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Daniel W. Lee, MD, University of Virginia
- Investigators
- Maxim Yankelevich, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02173093
- Sponsor's protocol ID
- 19031
- Other IDs
- NCI-2014-01149, 2013-171, P30CA022453
- Status last verified
- Jan 2019
- First submitted
- 22 Jun 2014
- Last updated
- 29 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.
PubMed 33986124
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study
- ClinicalTrials.gov ID
- NCT02173093
- Acronym / sponsor ID
- 19031
- Keywords
- Neuroblastoma, Solid tumor, Immunotherapy targeting GD2, Bispecific antibodies, Activated T cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2014
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 24 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (IL-2, GM-CSF, GD2Bi-aATC) | Experimental | Biological: IL-2, Biological: GD2Bi-aATC, Biological: GM-CSF, Other: laboratory evaluations of immune responsesPatients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy. |
Who may qualify
- Ages
- 13 months to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- 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:
- The presence of radiographically measurable disease immediately prior to start of Phase I immunotherapy is not an eligibility requirement in the following situations:
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IL-2Also: aldesleukin, Proleukin, recombinant human interleukin-2, recombinant interleukin-2Given SC | Biological | Treatment (IL-2, GM-CSF, GD2Bi-aATC) |
| GD2Bi-aATCAlso: GD2Bi-armed aATCGiven IV | Biological | Treatment (IL-2, GM-CSF, GD2Bi-aATC) |
| GM-CSFAlso: sargramostin, Leukine, ProkineGiven SC | Biological | Treatment (IL-2, GM-CSF, GD2Bi-aATC) |
| laboratory evaluations of immune responsesAlso: laboratory biomarker analysisCorrelative studies | Other | Treatment (IL-2, GM-CSF, GD2Bi-aATC) |
Primary outcome
Maximum tolerated dose (MTD) of GD2Bi-aATC
Time frame: 35 days
Safety of GD2Bi-aATC infusions is evaluated to determine MTD
2 secondary outcomes
Anti-tumor activity
Time frame: Up to 12 months
Immune responses after GD2Bi-aATC infusions
Time frame: Up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2019.
- Derived from this study: PubMed 33986124Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Holly Davis contact
Maxim Yankelevich principal investigator
Barbara Ann Karmanos Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IL-2, GD2Bi-aATC and GM-CSF in people with Disseminated Neuroblastoma and Recurrent Neuroblastoma, run by University of Virginia at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Holly Davis (haw5d@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of GD2Bi-aATC (time frame: 35 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02173093, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2019; AzTrials last refreshed its copy on 7 Nov 2026.