GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas (DIPG) & Spinal Diffuse Midline Glioma(DMG)

NCT04196413 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: IRB-52934PEDSCCT6005NCI-2020-058915R01CA263500-05
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to test whether CAR T cells targeting GD2 (GD2CART) can be successfully made and safely given to children and adults with H3K27M-mutant diffuse midline glioma (DMG). Eligible subjects may have DMG arising in the pons (called difuse intrinisic pontine glioma, DIPG), the spinal cord, or other areas of the brain such as a thalamus

Conditions

Glioma of Spinal Cord; Glioma of Brainstem

Outcome Measures

Primary Outcomes (3)

• Rate of successful manufacture of GD2CART using a retroviral vector in the Miltenyi CliniMACS Prodigy system

  The percentage of apheresis samples (fresh or frozen) will be determined for each dose cohort.

  14 days after apheresis

• Safety of the dose, route and schedule of GD2CART and lymphodepleting chemotherapy in subjects with H3K27M-mutant DMG

  Incidence and severity of dose limiting toxicities (DLTs) after initial dose of GD2.BB.z.iCasp9-CAR T cells (GD2CART) in each Arm, at each dose level tested by disease cohort

  28 days after infusion

• Safety of GD2CART at RP2D, route and schedule of GD2CART in expansion cohorts of subjects with H3K27M-mutant DMG

  Suspected adverse events and serious adverse events following chemotherapy preparative regimen and infusion of GD2CART."

  28 days after infusion

Secondary Outcomes (5)

• Radiographic Response Rate

  Time Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.

• Overall Survival (OS)

  Time Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.

• Progression-Free Survival (PFS)

  Time Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion

• Post-progression survival (PPS)

  ime Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion

• Measure resolution of toxicity

  72 hours of administration of AP1903

Study Arms (4)

ARM A

EXPERIMENTAL

GD2CART will be administered on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intravenously, after conditioning lymphodepletion chemotherapy regimen with cyclophosphamide and fludarabine * Dose Level -1: 3x10\^5 transduced T cells/kg(± 20%) * Dose Level 1: 1x10\^6 transduced T cells/kg (± 20%) * Dose Level 2: 3x10\^6 transduced T cells/kg (± 20%)

Drug: GD2 CAR T cells; Drug: Fludarabine; Drug: Cyclophosphamide

ARM B

EXPERIMENTAL

GD2CART will be administered on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intracerebroventricularly, without conditioning lymphodepletion chemotherapy * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%) * Dose Level 3: 100x10\^6 transduced T cells (±20%)

Drug: GD2 CAR T cells

ARM C

EXPERIMENTAL

GD2CART will be administered in escalating doses on Day 0 in hospitalized subjects with either DIPG or spinal DMG Intracerebroventricularly after administration of conditioning lymphodepletion chemotherapy regimen with cyclophosphamide and fludarabine * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%)

Drug: GD2 CAR T cells; Drug: Fludarabine; Drug: Cyclophosphamide

ARM D

EXPERIMENTAL

GD2CART will be administered in escalating doses on Day 0 in hospitalized subjects with either DIPG, spinal DMG, or high risk features. Intracerebroventricularly after administration of conditioning lymphodepletion chemotherapy regimen with rituximab, cyclophosphamide and fludarabine * Dose Level -1: 10x10\^6 transduced T cells (±20%) * Dose Level 1: 30x10\^6 transduced T cells (±20%) * Dose Level 2: 50x10\^6 transduced T cells (±20%)

Drug: GD2 CAR T cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab

Interventions

GD2 CAR T cells DRUG

Autologous T-Cells transduced with retroviral vector (14g2a-CD8.BB.z.iCasp9) expressing GD2-chimeric antigen receptor

ARM A; ARM B; ARM C; ARM D

Fludarabine DRUG

Fludarabine 30 mg/m2 per day IV for days -4, -3, -2

ARM A; ARM C; ARM D

Cyclophosphamide DRUG

Cyclophosphamide 500 mg/m2 per day IV for days -4, -3, -2

ARM A; ARM C; ARM D

Rituximab DRUG

First round: 750 mg/m2 per day IV for days -6 and -5. Subsequent rounds: 750 mg/m2 per day IV for day -5.

ARM D

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Disease Status: Diagnosis of H3K27M mutant diffuse midline glioma (DMG)
• H3K27M or H3K27I mutation. Confirmed by CLIA test.
• Age: Greater than or equal to 2 year of age and less than or equal to 60 years of age.
• Prior Therapy:
• At least 4 weeks following completion of standard upfront radiation therapy.
• At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy that requires 3 months.
• Dordaviprone (Modeyso), previously known as ONC201, may be taken as prior therapy but - just as with other anti-cancer medications - administration must cease at least 5 half-lives prior to enrollment
• Performance Status:
• Subjects \> 16 years of age: Karnofsky ≥ 60% OR Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Subjects ≤ 16 years of age: Lansky scale ≥ 60%.
• Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion) i. ANC ≥ 1000/uL ii. Platelet count ≥ 100,000/uL iii. Absolute lymphocyte count ≥ 150/uL iv. Hemoglobin ≥ 8 g/dL v. Adequate renal, hepatic, pulmonary and cardiac function defined as:
• \- Creatinine within institutional norms for age (i.e.
• ≤ 2 mg/dL in adults or according to table below in children \<18 years) OR creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
• Serum ALT/AST ≤ 3.0 ULN (grade 1)
• Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.

You may not qualify if:

• For Dose Escalation: Bulky tumor involvement of cerebellar vermis or hemispheres (pontocerebellar peduncles involvement is acceptable), or thalamic lesions that in the investigator's assessment place the subject at unacceptable risk for herniation.
• For Dose Expansion: Bulky disease that in the investigator's assessment place the subject at unacceptable risk for herniation. Thalamic DMG is permitted.
• Clinically significant swallowing dysfunction/dysphagia or prominent medullary dysfunction, as determined by the clinical investigator; or primary cervical cord tumors above C6/7 that represent a high risk of respiratory compromise, as determined by the clinical investigator.
• Current systemic corticosteroid therapy above physiologic replacement levels.
• Ongoing use of dietary supplements, alternative therapies or extreme diet modifications or any medication not approved by the investigators
• Prior CAR therapy.
• Prior immunomodulatory therapy, except for checkpoint inhibitor therapy after at least 3 month wash-out.
• Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable.
• Diagnosed ongoing infection with:
• HIV,
• Hepatitis B (HBsAg positive) or
• Hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Clinically significant systemic illness or medical condition (e.g. significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
• Women who are pregnant or breastfeeding.
• In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Sponsors & Collaborators

• California Institute for Regenerative Medicine (CIRM): collaborator
• Stanford University: lead
• CureSearch: collaborator
• National Cancer Institute (NCI): collaborator
• Alex's Lemonade Stand Foundation (ALSF): collaborator
• Parker Institute for Cancer Immunotherapy: collaborator

Study Sites (1)

Lucile Packard Children's Hospital (LPCH)

Stanford, California, 94304, United States

RECRUITING

MeSH Terms

Interventions

fludarabine; Cyclophosphamide; Rituximab

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michelle Monje

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley Jacobs, RN, BSN

CONTACT

650-497-7533; gd2cart@stanfordchildrens.org

Monica Reddy

CONTACT

(650) 736-2690; secure-sci-cto-neuro-crcs-nio@lists.stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 12, 2019
• Study Start: June 4, 2020
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2043
• Last Updated: January 26, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)