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

Launched by CITY OF HOPE MEDICAL CENTER · Jun 28, 2019

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment for patients with recurrent or hard-to-treat glioblastoma, a serious type of brain cancer. The study is looking at a special kind of immune therapy called IL13Ralpha2-CAR T cells, which are designed to target and attack glioblastoma cells. Some participants will receive these CAR T cells alone, while others will receive them along with two additional medications called nivolumab and ipilimumab. These medications help boost the body's immune response against the cancer. The goal is to see how well this treatment works and what side effects may occur.

To participate in the trial, patients must be at least 18 years old and have a confirmed diagnosis of glioblastoma that has come back or has not responded to previous treatments. They should also be in generally good health, with certain lab results meeting the study's requirements. Participants can expect to undergo treatment and regular check-ups to monitor their health and the effectiveness of the therapy. It's important for potential participants to discuss any health concerns with their doctors, as there are specific conditions and treatments that could exclude someone from joining the study.

Gender

ALL

Eligibility criteria

• • Inclusion Criteria Informed Consent and Willingness to Participate
• • 1. Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines.
• • 2. 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
• • 3. Ages ≥18 years
• • 4. KPS ≥ 60%, ECOG ≤ 2
• • 5. Life expectancy ≥ 4 weeks Nature of Illness and Illness Related Criteria
• • 6. 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.
• • 7. Relapsed/refractory disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and ≥ 12 weeks after completion of front-line radiation therapy.
• • 8. COH Clinical Pathology confirms IL13Rα2+ tumor expression by IHC at the initial tumor presentation or recurrent disease (H-score \> 50; reference Appendix B)
• • 9. 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.
• • 10. WBC \> 2000 /dl (or ANC ≥ 1,000/mm3)
• • 11. Platelets ≥ 75,000/mm3
• • 12. Fasting Blood glucose within ULN
• • 13. Total bilirubin ≤ 1.5 ULN
• • 14. AST ≤ 2.5x ULN
• • 15. ALT ≤ 2.5x ULN
• • 16. Serum creatinine ≤1.6 mg/dL
• • 17. O2 saturation ≥ 95% on room air
• • 18. Seronegative for HIV Ag/Ab combo, Hepatitis C Ab\*, active HBV (Surface Antigen Negative), Hepatitis A Virus IgM Antibody
• • \*If positive, Hepatitis C RNA quantitation must be performed.
• • 19. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be
• • 20. Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months after the last dose of nivolumab and/or 3 months after the last cycle of CAR T cells.
• • Exclusion Criteria Prior and concomitant therapies
• • 1. Prior CTLA-4, PD-1 or PD-L1 inhibitor therapy.
• • 2. Participant is steroid-dependent, requiring more than 6 mg of dexamethasone per day at the time of enrollment.
• • 3. Participant has not yet recovered from toxicities of prior therapy. Other illnesses or conditions
• • 4. History of or active autoimmune disease
• • 5. Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• • 6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• • 7. Active diarrhea
• • 8. Clinically significant uncontrolled illness
• • 9. Active infection requiring antibiotics
• • 10. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• • 11. Other active malignancy
• • 12. Females only: Pregnant or breastfeeding
• • 13. 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
• • 14. 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).