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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05650749
Other study ID # 22-019659
Secondary ID 22CT012
Status Recruiting
Phase Phase 1
First received
Last updated
Start date May 23, 2023
Est. completion date January 30, 2026

Study information

Verified date August 2023
Source Children's Hospital of Philadelphia
Contact Melissa Varghese
Phone 8455535358
Email Varghesem@chop.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date January 30, 2026
Est. primary completion date January 30, 2025
Accepts healthy volunteers No
Gender All
Age group 1 Year and older
Eligibility Inclusion Criteria: 1. Signed Informed Consent Form 2. = 1 year of age 3. Disease status 1. Patients must have high-risk neuroblastoma according to Children's Oncology Group risk classification at the time of study enrollment. 2. Histologically confirmed diagnosis of neuroblastoma that is recurrent/relapsed/persistent according to International Neuroblastoma Response Criteria 3. Patients must have evaluable or measurable disease at enrollment 4. Adequate organ function 5. Adequate performance status defined as Lanksy or Karnofsky performance score =60. 6. Subjects of reproductive potential must agree to use acceptable birth control methods. Exclusion Criteria: 1. Patients with active hepatitis B or active hepatitis C. 2. Patients with HIV infection. 3. Patients with uncontrolled active infection 4. Patients with primary or acquired immunodeficiency disorder. 5. 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. 6. Patients with actively progressing Central Nervous System metastases, including parenchymal or leptomeningeal involvement. 7. Active medical disorder that, in the opinion of the investigator, would substantially increase. the risk of uncontrollable Cytokine Release Syndrome and/or neurotoxicity. 8. 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. 9. Patients who have received any live vaccines within 30 days prior to enrollment. 10. Pregnant or nursing (lactating) women.

Study Design


Intervention

Biological:
GPC2 CAR T cells
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.

Locations

Country Name City State
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania

Sponsors (4)

Lead Sponsor Collaborator
Stephan Grupp MD PhD Children's Hospital of Philadelphia, Tmunity Therapeutics, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 5 years
Primary 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. 5 years
Secondary 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 5 years
Secondary 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. 5 years
Secondary 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 5 years
Secondary 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. 5 years
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