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GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults

ConditionsMedulloblastomaCentral Nervous System Embryonal TumorRefractory MedulloblastomaRecurrent MedulloblastomaPediatric Brain TumorEmbryonal Tumor With Multilayered Rosettes (ETMR)PineoblastomaAtypical Teratoid/Rhabdoid Tumor (ATRT) of the CNSCNS NeuroblastomaFOXR2-activatedChildhood
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age1-30
SponsorStanford University

About this trial

This is a single-site, open-label Phase I treatment study evaluating the manufacturing feasibility and safety of chimeric antigen receptor (CAR) T cells targeting the oncofetal protein Glypican-2 (GPC2) in pediatric and young adult patients with recurrent or refractory (R/R) medulloblastoma. Subjects with other non-medulloblastoma CNS embryonal tumors may enroll.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)

Embryonal Tumor with Multilayered Rosettes (ETMR)

Pineoblastoma

Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS

Disqualifiers

Any patient with metastatic disease OUTSIDE the CNS.

Unwilling or unable, in the investigator's judgement, to have a CSF reservoir (Ommaya or Rickham) placed. Does not apply to subjects who have a pre-existing device suitable for ICV delivery of CAR T cells and ICP monitoring.

Clinical evidence of active/on-going significant increased intracranial pressure (i.e., impending herniation) or uncontrolled seizures.

Prior receipt of a chimeric antigen receptor (CAR)-based therapy.

Trial design

Design model

Sequential

Treatments tested in this trial

  • GPC2-CAR T cells

    Genetic

    Autologous T cells transduced with a retroviral vector encoding a second-generation GPC2-targeted chimeric antigen receptor (GPC2-CAR), administered intracerebroventricularly. Up to 16 doses (cycles) are administered using an intrapatient dose-escalation strategy. Cycle 2 may occur no earlier than Day 28 following Cycle 1, and Cycles 3 through 16 may occur as early as Day 22 following the preceding cycle.

  • Fludarabine

    Drug

    Participants who meet eligibility criteria for lymphodepletion chemotherapy will receive fludarabine 30 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing \<12 kg will receive protocol-specified dose adjustments.

  • Cyclophosphamide

    Drug

    Participants who meet eligibility criteria for lymphodepletion chemotherapy will receive cyclophosphamide 500 mg/m²/day administered intravenously on Days -4, -3, and -2 prior to study treatment. Participants weighing \<12 kg will receive protocol-specified dose adjustments.

Treatment groups

18 Participants
are divided into 1 treatment group
Group A: GPC2-CAR T Cell TherapyExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Manufacturing Feasibility

Proportion of manufacturing attempts that result in at least one dose of GPC2-CAR T cells that meet the IND release criteria and protocol-specified dose.

Time frame
Up to 6 months post-leukapheresis
2

Incidence of Dose Limiting Toxicities (DLTs)

Number and severity of DLTs following GPC2-CAR T cell administration at each dose level using protocol-defined criteria.

Time frame
Within first 28-day treatment cycle per dose level

Secondary outcomes

1

Objective Response Rate (ORR)

Percentage of subjects achieving a protocol-defined response (complete response, partial response, or stable disease) based on imaging and neurological exam.

Time frame
Up to 2 years post-infusion
2

Progression-Free Survival (PFS)

Time from enrollment to radiographic disease progression.

Time frame
Up to 2 years
3

Overall Survival (OS)

Time from initial diagnosis to death from any cause.

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

Source ClinicalTrials.gov
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