IL13Ra2-CAR T Cells With or Without Nivolumab and Ipilimumab in Treating Patients With GBM

NCT04003649 | Active Not Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 18251NCI-2018-02764R01CA236500Bristol-Meyers SquibbGateway for Cancer Research
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and how well IL13Ralpha2-CAR T cells work when given alone or together with nivolumab and ipilimumab in treating patients with glioblastoma that has come back (recurrent) or does not respond to treatment (refractory). Biological therapies, such as IL13Ralpha2-CAR T cells, use substances made from living organisms that may attack specific glioma cells and stop them from growing or kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving IL13Ralpha2-CAR T cells and nivolumab together may work better in treating patients with glioblastoma.

Conditions

Recurrent Glioblastoma; Refractory Glioblastoma

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  Will assess dose limiting toxicity and all toxicities. Toxicity is the primary endpoint and will be assessed using the National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Rates and associated 95% Clopper and Pearson binomial confidence limits (95% confidence interval \[CI\]) will be estimated for participants' experiencing dose limiting toxicity (DLT) during neoadjuvant treatment period (DLT period 1), during adjuvant treatment period (DLT period 2), neo-adjuvant and adjuvant feasibility, as well as survival at 9 months. All toxicities and side effects will be summarized in tables by dose, time period, organ, and severity.

  Up to 15 years

• Dose-limiting toxicity (DLT)

  A toxicity that causes side effects that are serious enough to prevent an increase in dose or level of that treatment.

  Up to 28 days

• Feasibility (neoadjuvant therapy)

  As measured by the ability of patients receive ipilimumab/nivolumab (\> 80% of the assigned doses) and undergo undergo surgery so that they can go on to receive the first dose of CAR T cells.

  Up to 14 days

• Feasibility (adjuvant therapy)

  Defined as the ability of patients to complete 4 cycles of CAR T infusions (\> 80% of the assigned dose) and 2 doses of nivolumab.

  Up to 28 days

• Overall Survival

  The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

  At 9 months

Secondary Outcomes (12)

• T cell levels

  Up to 15 years

• Cytokine levels in TCF, PB, and CSF

  Up to 15 years

• Disease response

  Up to 15 years

• Time to progression

  Up to 15 years

• Overall survival (OS)

  Up to 15 years

Study Arms (3)

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells)

EXPERIMENTAL

Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab IV over 90 minutes on day -14. Patients then receive IL13Ralpha2 CAR T cells infusion over 5 minutes via Rickham catheter (ICV/intracranital ICT) every week and nivolumab IV over 30 minutes every other week. Treatment repeats weekly for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After cycle 4, patients may receive additional CAR T cells weekly and nivolumab IV every other week or monthly at the discretion of the principal investigator and oncologist.

Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Biological: Ipilimumab; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (nivolumab, IL13Ra2 CAR T cells)

EXPERIMENTAL

Patients receive IL13Ralpha2 CAR T cells infusion over 5 minutes via Rickham catheter (ICV/ICT) every week and nivolumab IV over 30 minutes every other week. Treatment repeats weekly for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After cycle 4, patients may receive additional CAR T cells weekly and nivolumab IV every other week or monthly at the discretion of the principal investigator and oncologist.

Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm III (IL13Ra2 CAR T cells)

EXPERIMENTAL

Patients receive IL13Ralpha2 CAR T cells infusion over 5 minutes via Rickham catheter (ICV/ICT) every week. Treatment repeats weekly for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After cycle 4, patients may receive additional CAR T cells weekly at the discretion of the principal investigator and oncologist.

Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells BIOLOGICAL

Given ITV/ITC

Also known as: IL13 [EQ]BBzeta/truncated CD19[t]+ Naive and Memory T Cells, IL13 [EQ]BBzeta/truncated CD19[t]+ TN/MEM Cells, IL13Ra2-specific-hinge-optimized-4-1BB-CAR/truncated CD19-expressing Autologous TN/MEM Lymphocytes

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells); Arm II (nivolumab, IL13Ra2 CAR T cells); Arm III (IL13Ra2 CAR T cells)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells); Arm II (nivolumab, IL13Ra2 CAR T cells)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells); Arm II (nivolumab, IL13Ra2 CAR T cells); Arm III (IL13Ra2 CAR T cells)

Questionnaire Administration OTHER

Ancillary studies

Arm I (nivolumab, ipilimumab, IL13Ralpha2 CAR T cells); Arm II (nivolumab, IL13Ra2 CAR T cells); Arm III (IL13Ra2 CAR T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines.
• \. Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with Study PI approval. Age Criteria, Performance status
• \. Ages ≥18 years
• \. KPS ≥ 60%, ECOG ≤ 2
• \. Life expectancy ≥ 4 weeks Nature of Illness and Illness Related Criteria
• \. Histologically confirmed diagnosis of WHO classification grade IV GBM, or has a prior histologicallyconfirmed diagnosis of a grade II or III glioma and now has radiographic progression consistent with a grade IV GBM after completing standard therapy.
• \. Relapsed/refractory disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and ≥ 12 weeks after completion of front-line radiation therapy.
• \. COH Clinical Pathology confirms IL13Rα2+ tumor expression by IHC at the initial tumor presentation or recurrent disease (H-score \> 50; reference Appendix B)
• \. Participants with a known history of congestive heart failure (CHF) or cardiac symptoms consistent with NYHA classification III-IV within 6 months prior to Day 1 of protocol treatment, cardiomyopathy, myocarditis, Myocardial Infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an EKG and Echocardiogram (ECHO) performed within 42 days prior to registration and as clinically indicated while on treatment. Clinical Laboratory and Organ Function Criteria (To be performed within 14 days prior to leukapheresis unless otherwise stated.
• \. WBC \> 2000 /dl (or ANC ≥ 1,000/mm3)
• \. Platelets ≥ 75,000/mm3
• \. Fasting Blood glucose within ULN
• \. Total bilirubin ≤ 1.5 ULN
• \. AST ≤ 2.5x ULN
• \. ALT ≤ 2.5x ULN

You may not qualify if:

• \. Prior CTLA-4, PD-1 or PD-L1 inhibitor therapy.
• \. Participant is steroid-dependent, requiring more than 6 mg of dexamethasone per day at the time of enrollment.
• \. Participant has not yet recovered from toxicities of prior therapy. Other illnesses or conditions
• \. History of or active autoimmune disease
• \. Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• \. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• \. Active diarrhea
• \. Clinically significant uncontrolled illness
• \. Active infection requiring antibiotics
• \. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• \. Other active malignancy
• \. Females only: Pregnant or breastfeeding
• \. Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures. Noncompliance
• \. Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator
• Gateway for Cancer Research: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Interleukin-13; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biomarkers

Study Officials

• Behnam Badie, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 23, 2018
• First Posted: July 1, 2019
• Study Start: December 2, 2019
• Primary Completion (Estimated): April 13, 2027
• Study Completion (Estimated): April 13, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)