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

ConditionsGlioma of Spinal CordGlioma of Brainstem
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2-60
SponsorStanford University

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

At least 4 weeks following completion of standard upfront radiation therapy.

Disqualifiers

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.

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

Trial design

Design model

Single group

Treatments tested in this trial

  • GD2 CAR T cells

    Drug

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

  • Fludarabine

    Drug

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

  • Cyclophosphamide

    Drug

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

  • 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.

Treatment groups

97 Participants
are divided into 4 treatment groups
Group A: ARM AExperimental treatment 3 interventions
Group B: ARM BExperimental treatment 1 intervention
Group C: ARM CExperimental treatment 3 interventions
Group D: ARM DExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
14 days after apheresis
2

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

Time frame
28 days after infusion
3

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."

Time frame
28 days after infusion

Secondary outcomes

1

Radiographic Response Rate

Radiographic Response will be evaluated using the RANO 2.0 tumor response criteria.

Time frame
Time Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.
2

Overall Survival (OS)

Overall survival (OS) is defined as the time from date of initial diagnosis to date of death from any cause. Treatment OS is defined as the time from Cycle 1 Day 0 to date of death from any cause.

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

Progression-Free Survival (PFS)

PFS is defined as the time from the start of the lymphodepleting chemotherapy preparative regimen to the date of radiographic progression or death from any cause.

Time frame
Time Frame: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion
4

Post-progression survival (PPS)

PPS is measured for each subject with DIPG as OS minus PFS, and for each patient with recorded progression as OS minus Time to Progression (TTP)

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

Other outcomes

Sponsors and contacts

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

Stanford University

Lead sponsor

California Institute for Regenerative Medicine (CIRM)

Collaborator

CureSearch

Collaborator

National Cancer Institute (NCI)

Collaborator

Alex's Lemonade Stand Foundation

Collaborator

Parker Institute for Cancer Immunotherapy

Collaborator

Source ClinicalTrials.gov
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