- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05835687
Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors
Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Jean Laboe, MSN, RN
- Phone Number: 901-595-1693
- Email: jean.laboe@stjude.org
Study Contact Backup
- Name: Tabatha E. Doyle, RN
- Phone Number: 901-595-2544
- Email: tabatha.doyle@stjude.org
Study Locations
-
-
Tennessee
-
Memphis, Tennessee, United States, 38105
- Recruiting
- St. Jude Children's Research Hospital
-
Contact:
- Tabatha E. Doyle, RN
- Phone Number: 901-595-2544
- Email: tabatha.doyle@stjude.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria: Screening Eligibility
- Age ≤ 21 years of age
- Primary CNS tumor with measurable disease
- For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor
For Cohort B, must meet one of the following criteria:
- Adequate tumor tissue from primary tumor resection or biopsy for central pathology review
- Has presumptive/suspected brainstem high-grade neoplasm with available imaging for central imaging review
- Life expectancy of > 12 weeks
- Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
Exclusion Criteria: Screening Eligibility All Participants
1. Clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure
Inclusion Criteria: Procurement and T-cell Production Eligibility
- Age ≤ 21 years of age
Primary CNS tumor with measurable disease and meets criteria for either Cohort A or B:
- Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive
Cohort B: brainstem high-grade neoplasm AND tumor is:
- B7-H3 positive
- OR H3K27-altered diffuse midline glioma
- OR radiographically-confirmed classic/typical DIPG
- Estimated life expectancy of >12 weeks
- Karnofsky or Lansky performance score ≥50
- Participant of childbearing/child-fathering potential agrees to use contraception
For females of childbearing age:
- Not pregnant with negative serum pregnancy test
- Not lactating with intent to breastfeed
- Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment
- The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter
- At least 30 days from most recent cell infusion prior to enrollment.
- All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day
- Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program
- Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
Exclusion Criteria: Procurement and T-cell Production Eligibility
- Participant has a non-programmable ventricular shunt that could compromise study therapy
- Known primary immunodeficiency or acquired immunodeficiency.
- Known HIV positivity
- Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).
- Rapidly progressive disease
- Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.
- Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.
Inclusion Criteria: Treatment Eligibility
Cohort A
- Relapsed/refractory non-brainstem CNS primary tumor
- Tumor must be considered B7-H3 positive
Cohort B
Brainstem high-grade neoplasm. Must meet one of the following criteria
- Tumor is considered B7-H3 positive
- H3K27-altered diffuse midline glioma
- Radiographically-confirmed classic/typical DIPG
- Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy
All participants
- Age ≤ 21 years old
- Primary CNS tumor with measurable disease
- Available autologous T-cell product that has met GMP release criteria
- Participant has a CNS reservoir catheter (e.g., Ommaya)
- Participant is ≥ 5 days from CNS surgery, including catheter placement
The following treatments must be discontinued for the specified duration prior to treatment enrollment:
- Radiation therapy: ≥ 6 weeks
- Bevacizumab: ≥ 28 days
- Cytotoxic chemotherapy: ≥ 21 days
- Biologic agents: ≥ 7 days
- Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)
- Cellular therapy: ≥ 30 days
- Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter)
- Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m^2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.
- Estimated life expectancy of >8 weeks
- Karnofsky or Lansky performance score ≥ 50
- Echocardiogram with a left ventricular ejection fraction > 50%
- Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL/min/1.73m^2.
- Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.
- Total Bilirubin ≤3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.
- Hemoglobin >8.0 g/dL (can be transfused).
- Platelet count >50,000/mm^3 (can be transfused).
- Absolute neutrophil count (ANC) ≥1000/uL.
- Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.
- Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy.
- Male participants of child-fathering potential agree to use contraception
Female participants of childbearing potential:
- Negative serum pregnancy test within 7 days prior to infusion
- Not lactating with intent to breastfeed
- If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom
- Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
Exclusion Criteria: Treatment Eligibility-All Participants
- Participant has a non-programmable ventricular shunt that could compromise study therapy
- Known primary immunodeficiency or acquired immunodeficiency.
- Known HIV positivity
- Severe intercurrent bacterial, viral or fungal infection
- Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry
- Receiving therapy as outlined above during the 'wash-out' period
- Rapidly progressing disease
- Received any live vaccines within 30 days
- Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments
- Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (relapsed/refractory CNS tumors)
Patients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.
|
Autologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells).
Six (6) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.
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Experimental: Arm B (brainstem high-grade neoplasms)
Patients with high-grade neoplasms
|
Autologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells).
Six (6) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose (MTD)
Time Frame: Eight (8) weeks after the first B7-H3-CAR T-cell infusion or 7 days after the sixth B7-H3-CAR T cell infusion, whichever is longer
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To determine the maximum tolerated dose for the locoregional delivery of autologous B7-H3-CAR T cells in patients with recurrent/refractory B7-H3- positive primary CNS tumors (Cohort A) or high-grade brainstem neoplasms (Cohort B).
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Eight (8) weeks after the first B7-H3-CAR T-cell infusion or 7 days after the sixth B7-H3-CAR T cell infusion, whichever is longer
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sustained objective radiographic response
Time Frame: Eight (8) weeks post B7-H3-CAR T-cell infusion
|
To assess the efficacy, defined as sustained objective response (a partial response (PR) or complete response (CR) sustained over 8 weeks) by iRANO criteria observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3-positive primary CNS tumors (Cohort A) or high-grade brainstem neoplasms (Cohort B).
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Eight (8) weeks post B7-H3-CAR T-cell infusion
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Collaborators and Investigators
Investigators
- Principal Investigator: Christopher DeRenzo, MD, St. Jude Children's Research Hospital
- Principal Investigator: Kelsey Bertrand, MD, MSc, St. Jude Children's Research Hospital
- Principal Investigator: Giedre Krenciute, PhD, St. Jude Children's Research Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neoplasms, Complex and Mixed
- Neuroectodermal Tumors, Primitive
- Glioblastoma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Ependymoma
- Medulloblastoma
- Rhabdoid Tumor
Other Study ID Numbers
- Loc3CAR
- NCI-2023-02484 (Registry Identifier: NCI Clinical Trial Registration Program)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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