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B7-H3-CAR T Cells for Pediatric CNS Tumors

Sponsor
St. Jude Children's Research Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05835687
Collaborator
(none)
36
Enrollment
1
Location
2
Arms
58.2
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with brainstem high-grade neoplasms. Participants will receive six (6) B7-H3-CAR T cell infusions over an 8 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.

Condition or Disease Intervention/Treatment Phase
  • Drug: B7-H3-CAR T cells
 Phase 1

Detailed Description

Treatment on this study includes six (6) B7-H3-CAR T cell infusions over an 8 week period. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells using a 3+3 study design and an 8 week evaluation period. The total study duration will be 1 year, at which point patients will enroll on our existing institutional long-term follow up protocol.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
36 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors
Actual Study Start Date :
Apr 25, 2023
Anticipated Primary Completion Date :
Mar 1, 2028
Anticipated Study Completion Date :
Mar 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (relapsed/refractory CNS tumors)

Patients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.

Drug: B7-H3-CAR T cells
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.
Experimental: Arm B (brainstem high-grade neoplasms)

Patients with high-grade neoplasms

Drug: B7-H3-CAR T cells
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.

Outcome Measures

Primary Outcome Measures

  1. Maximum tolerated dose (MTD) [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]

    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).

Secondary Outcome Measures

  1. Sustained objective radiographic response [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria: Screening Eligibility

  1. Age ≤ 21 years of age

  2. Primary CNS tumor with measurable disease

  3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor

  4. For Cohort B, must meet one of the following criteria:

  • Adequate tumor tissue from for central pathology review

  • Brainstem high-grade neoplasm with available imaging for central review

  1. Life expectancy of > 12 weeks

  2. 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 that could compromise their ability to tolerate protocol therapy or would interfere with study procedure Inclusion Criteria: Procurement and T-cell Production Eligibility

  2. Age ≤ 21 years of age

  3. 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

  1. Estimated life expectancy of >12 weeks

  2. Karnofsky or Lansky performance score ≥50

  3. Participant of childbearing/child-fathering potential agrees to use contraception

  4. For females of childbearing age:

  • Not pregnant with negative serum pregnancy test

  • Not lactating with intent to breastfeed

  1. Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment

  2. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter

  3. At least 30 days from most recent cell infusion prior to enrollment.

  4. 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

  5. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program

  6. 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

  1. Participant has a non-programmable ventricular shunt that could compromise study therapy

  2. Known primary immunodeficiency or acquired immunodeficiency.

  3. Known HIV positivity

  4. Severe intercurrent bacterial, viral or fungal infection

  5. Rapidly progressive disease

  6. 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

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

  1. Age ≤ 21 years old

  2. Primary CNS tumor with measurable disease

  3. Available autologous T-cell product that has met GMP release criteria

  4. Participant has a CNS reservoir catheter (e.g., Ommaya)

  5. Participant is ≥ 5 days from CNS surgery, including catheter placement

  6. 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/m2/day

  1. Estimated life expectancy of >8 weeks

  2. Karnofsky or Lansky performance score ≥ 50

  3. Echocardiogram with a left ventricular ejection fraction > 50%

  4. Adequate organ function

  5. Adequate laboratory values

  6. Taking anti-seizure medication, or agrees to initiate anti-seizure medication

  7. Recovered from acute toxicities from prior therapy

  8. Male participants of child-fathering potential agree to use contraception

  9. 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

  1. Participant has a non-programmable ventricular shunt that could compromise study therapy

  2. Known primary immunodeficiency or acquired immunodeficiency.

  3. Known HIV positivity

  4. Severe intercurrent bacterial, viral or fungal infection

  5. 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

  6. Receiving therapy outlined above during the 'wash-out' period

  7. Rapidly progressing disease

  8. Received any live vaccines within 30 days

  9. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 St. Jude Children's Research Hospital Memphis Tennessee United States 38105

Sponsors and Collaborators

  • St. Jude Children's Research Hospital

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT05835687
Other Study ID Numbers:
  • Loc3CAR
  • NCI-2023-02484
First Posted:
Apr 28, 2023
Last Update Posted:
May 5, 2023
Last Verified:
May 1, 2023
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Glioblastoma
Glioma
Ependymoma
Medulloblastoma
Rhabdoid Tumor
Central Nervous System Neoplasms
Nervous System Neoplasms

Study Results

No Results Posted as of May 5, 2023