Using IL13Ra2-CAR T cells with or without immune therapy for treating recurrent glioblastoma
A Phase 1 Study to Evaluate IL13Rα2-Targeted Chimeric Antigen Receptor (CAR) T Cells Combined With Checkpoint Inhibition for Patients With Resectable Recurrent Glioblastoma
This study is testing a new type of immune therapy using IL13Ra2-CAR T cells, with or without additional treatments, to see if it can help people with recurring glioblastoma feel better and live longer.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | nivolumab, CAR T, radiation, ipilimumab, Immunotherapy |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT04003649 on ClinicalTrials.gov |
What this trial studies
This phase I trial investigates the safety and effectiveness of IL13Ralpha2-CAR T cells, both alone and in combination with the immune checkpoint inhibitors nivolumab and ipilimumab, in patients with recurrent or refractory glioblastoma. The study aims to assess the feasibility of these treatments and their impact on tumor response, survival rates, and quality of life. Participants will be monitored for side effects and the persistence of CAR T cells in various bodily fluids. The trial will also evaluate cytokine levels and overall disease progression.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of recurrent or refractory glioblastoma.
Not a fit: Patients with non-recurrent glioblastoma or those who do not meet the eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new, effective treatment option for patients with difficult-to-treat glioblastoma.
How similar studies have performed: Other studies have shown promise with CAR T cell therapies in various cancers, but this specific combination approach is novel.
Eligibility criteria
Show full inclusion / exclusion 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).
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Behnam Badie, MD — City of Hope Medical Center
- Study coordinator: Behnam Badie, MD
- Email: BBehnam@coh.org
- Phone: 6263598111
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.