search
Back to results

GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma (GPC2)

Primary Purpose

Refractory Neuroblastoma, Relapsed Neuroblastoma, High-risk Neuroblastoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GPC2 CAR T cells
Sponsored by
Stephan Grupp MD PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Neuroblastoma

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed Informed Consent Form ≥ 1 year of age Disease status Patients must have high-risk neuroblastoma according to Children's Oncology Group risk classification at the time of study enrollment. Histologically confirmed diagnosis of neuroblastoma that is recurrent/relapsed/persistent according to International Neuroblastoma Response Criteria Patients must have evaluable or measurable disease at enrollment Adequate organ function Adequate performance status defined as Lanksy or Karnofsky performance score ≥60. Subjects of reproductive potential must agree to use acceptable birth control methods. Exclusion Criteria: Patients with active hepatitis B or active hepatitis C. Patients with HIV infection. Patients with uncontrolled active infection Patients with primary or acquired immunodeficiency disorder. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well. Patients with actively progressing Central Nervous System metastases, including parenchymal or leptomeningeal involvement. Active medical disorder that, in the opinion of the investigator, would substantially increase. the risk of uncontrollable Cytokine Release Syndrome and/or neurotoxicity. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis. Patients who have received any live vaccines within 30 days prior to enrollment. Pregnant or nursing (lactating) women.

Sites / Locations

  • Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dose Escalation Arm

Dose Expansion Arm

Arm Description

The dose escalation arm will determine the maximum tolerated dose of GPC2 CAR T cells using a standard 3+3 trial design.

If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to GPC2 CAR T cells and further characterize the safety profile of GPC2 CAR T cells.

Outcomes

Primary Outcome Measures

Determine the Maximum Tolerated Dose of GPC2 CAR T cells
The Maximum Tolerated Dose of GPC2 CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.
Frequency of Adverse Events Following GPC2 CAR T cell administration
Assess the frequency and severity of treatment related adverse events following administration of GPC2 CAR T cells.

Secondary Outcome Measures

Manufacturing Feasibility of GPC2 CAR T cells
Manufacturing Feasibility will be evaluated as the Percentage of patients with GPC2 CAR T cell products that meet release criteria
Persistence of GPC2 CAR T cells
Persistence of GPC2 CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis of whole blood to detect and quantify survival of GPC2 CAR T cells over time.
Preliminarily define the clinical activity of GPC2 CAR T in patients with relapsed or refractory neuroblastoma
Overall Response Rate will be determined based on international Neuroblastoma Response Criteria
Severity of Adverse Events Following GPC2 CAR T cell administration.
The safety of GPC2 CAR T cell therapy reinfusions will be measured by the monitoring the frequency and severity of adverse events after multipleGPC2 CAR T cells infusions.

Full Information

First Posted
December 6, 2022
Last Updated
August 28, 2023
Sponsor
Stephan Grupp MD PhD
Collaborators
Children's Hospital of Philadelphia, Tmunity Therapeutics, University of Pennsylvania
search

1. Study Identification

Unique Protocol Identification Number
NCT05650749
Brief Title
GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma
Acronym
GPC2
Official Title
Phase 1 Trial of GPC2-Directed Chimeric Antigen Receptor Autologous T Cells (GPC2 CAR T) for Relapsed or Refractory Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
January 30, 2025 (Anticipated)
Study Completion Date
January 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stephan Grupp MD PhD
Collaborators
Children's Hospital of Philadelphia, Tmunity Therapeutics, University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a first in human dose escalation trial to determine the safety of administering GPC2 CAR T cells in patients with advanced neuroblastoma.
Detailed Description
Despite the use of intensive multimodal chemoradiotherapy, surgery, autologous stem cell transplant and disialoganglioside antigen (GD2)-targeted immunotherapy for the treatment of patients with high-risk neuroblastoma, approximately 60% of children still die from this disease and survivors suffer lifelong treatment related comorbidities. For patients who suffer a relapse after receiving therapy with standard of care multimodality treatment, there are no known curative options. Glypican 2 (GPC2) is highly expressed on the plasma membrane of most high-risk neuroblastomas, is further enriched in the tumor stem cell compartment, but is not expressed at significant levels on normal tissues, making it an ideal target for immune directed therapies. To therapeutically leverage GPC2's differential expression, a GPC2-directed CAR T cell therapy that potently inhibits the growth of neuroblastoma patient-derived xenografts has been developed. This investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of GPC2 CAR T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Neuroblastoma, Relapsed Neuroblastoma, High-risk Neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Arm
Arm Type
Experimental
Arm Description
The dose escalation arm will determine the maximum tolerated dose of GPC2 CAR T cells using a standard 3+3 trial design.
Arm Title
Dose Expansion Arm
Arm Type
Experimental
Arm Description
If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to GPC2 CAR T cells and further characterize the safety profile of GPC2 CAR T cells.
Intervention Type
Biological
Intervention Name(s)
GPC2 CAR T cells
Intervention Description
The GPC2 CAR T investigational product is comprised of autologous human T cells that have been genetically modified to express a GPC2-targeting chimeric antigen receptor (CAR) transgene.
Primary Outcome Measure Information:
Title
Determine the Maximum Tolerated Dose of GPC2 CAR T cells
Description
The Maximum Tolerated Dose of GPC2 CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.
Time Frame
5 years
Title
Frequency of Adverse Events Following GPC2 CAR T cell administration
Description
Assess the frequency and severity of treatment related adverse events following administration of GPC2 CAR T cells.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Manufacturing Feasibility of GPC2 CAR T cells
Description
Manufacturing Feasibility will be evaluated as the Percentage of patients with GPC2 CAR T cell products that meet release criteria
Time Frame
5 years
Title
Persistence of GPC2 CAR T cells
Description
Persistence of GPC2 CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis of whole blood to detect and quantify survival of GPC2 CAR T cells over time.
Time Frame
5 years
Title
Preliminarily define the clinical activity of GPC2 CAR T in patients with relapsed or refractory neuroblastoma
Description
Overall Response Rate will be determined based on international Neuroblastoma Response Criteria
Time Frame
5 years
Title
Severity of Adverse Events Following GPC2 CAR T cell administration.
Description
The safety of GPC2 CAR T cell therapy reinfusions will be measured by the monitoring the frequency and severity of adverse events after multipleGPC2 CAR T cells infusions.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed Informed Consent Form ≥ 1 year of age Disease status Patients must have high-risk neuroblastoma according to Children's Oncology Group risk classification at the time of study enrollment. Histologically confirmed diagnosis of neuroblastoma that is recurrent/relapsed/persistent according to International Neuroblastoma Response Criteria Patients must have evaluable or measurable disease at enrollment Adequate organ function Adequate performance status defined as Lanksy or Karnofsky performance score ≥60. Subjects of reproductive potential must agree to use acceptable birth control methods. Exclusion Criteria: Patients with active hepatitis B or active hepatitis C. Patients with HIV infection. Patients with uncontrolled active infection Patients with primary or acquired immunodeficiency disorder. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well. Patients with actively progressing Central Nervous System metastases, including parenchymal or leptomeningeal involvement. Active medical disorder that, in the opinion of the investigator, would substantially increase. the risk of uncontrollable Cytokine Release Syndrome and/or neurotoxicity. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis. Patients who have received any live vaccines within 30 days prior to enrollment. Pregnant or nursing (lactating) women.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melissa Varghese
Phone
8455535358
Email
Varghesem@chop.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Yael Mosse, MD
Email
mosse@chop.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Wray, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Varghese
Phone
845-553-5358
Email
Varghesem@chop.edu
First Name & Middle Initial & Last Name & Degree
Lisa Wray, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma

We'll reach out to this number within 24 hrs