RECRUITING

CAR T Cells After Lymphodepletion for the Treatment of IL13Rα2 Positive Recurrent or Refractory Brain Tumors in Children

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Conditions

Malignant Brain NeoplasmRecurrent Malignant Brain NeoplasmRefractory Malignant Brain Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial investigates the side effects of chemotherapy and cellular immunotherapy in treating children with IL13Ralpha2 positive brain tumors that have come back after a period of improvement (recurrent) or do not respond to treatment (refractory). Cellular immunotherapy (IL13(EQ)BBzeta/CD19t+ T cells) are brain-tumor specific cells that may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Many patients with brain tumor respond to treatment, but then the tumor starts to grow again. Giving chemotherapy in combination with cellular immunotherapy may kill more tumor cells and improve the outcome of treatment.

Official Title

Phase I Study of Cellular Immunotherapy Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Children With Recurrent/Refractory Malignant Brain Tumors

Quick Facts

Study Start:2020-12-04
Study Completion:2025-08-24
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04510051

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Years to 25 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant and/or legally authorized representative.
  2. * Assent, when appropriate, will be obtained per institutional guidelines
  3. * Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  4. * Karnofsky Performance Status (KPS) \>= 60% except for loss of mobility due to disease involvement; e.g., confinement to a wheelchair due to spinal cord compression
  5. * Life expectancy \> 4 weeks
  6. * Participant has a prior histologically-confirmed malignant brain neoplasm and has progressed after prior conventional therapy
  7. * Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial conventional therapy (including initial radiation therapy)
  8. * City of Hope (COH) clinical pathology confirms IL13Ralpha2+ tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50)
  9. * If the participant has a shunt, it must be programmable and the participant must be able to tolerate the shunt being switched off for at least 2 consecutive days
  10. * Platelets \>= 50,000/mm\^3 (performed within 6 weeks of signing the main informed consent)
  11. * Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 6 weeks of signing the main informed consent)
  12. * Aspartate transaminase (AST) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent)
  13. * Alanine transferase (ALT) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent)
  14. * Creatinine clearance of \>= 75mL/min/1.73m\^2 (performed within 6 weeks of signing the main informed consent)
  15. * Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)\* and active HBV (surface antigen negative) (performed within 6 weeks of signing the main informed consent)
  16. * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  17. * Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 6 weeks of signing the main informed consent)
  18. * 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 6 months after the last dose of protocol therapy.
  19. * Childbearing potential defined as not being surgically sterilized (males and females) or have not been free, once initiated, from menses for \> 1 year (females only)
  20. * ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR COLLECTION (PBMC) COLLECTION
  21. * Research participant must not require more than 0.1mg/kg/day total dose (0.03mg/kg/dose three times per day, max of 6mg/day) of Dexamethasone on the day of peripheral blood mononuclear cell (PBMC) collection
  22. * Research participant must have appropriate venous access
  23. * At least 2 weeks must have elapsed since the research participant received his/her last dose of prior targeted agents, chemotherapy or radiation
  24. * Note: If a research participant weighs less than 50kgs, the study team should provide the Donor Apheresis Center (DAC) with the participant's current weight so that institutional guidelines can be followed
  25. * ELIGIBILITY TO PROCEED WITH INDWELLING CENTRAL NERVOUS SYSTEM (CNS) CATHETER PLACEMENT
  26. * Serum creatinine \< 1.6 mg/dL
  27. * White blood cell (WBC) \>= 2,000/dL
  28. * Absolute neutrophil count (ANC) \>= 1,000
  29. * Platelets \> 50,000/dL
  30. * International normalized ratio =\< 1.3
  31. * Bilirubin \< 1.5 mg/dL
  32. * Alanine transferase (ALT) and aspartate transaminase (AST) \< 2 x upper limits of normal
  33. * KPS \>= 60% except for loss of mobility due to disease involvement; e.g., confinement to a wheelchair due to spinal cord compression
  34. * Second-line radiation therapy (post-leukapheresis) completed at least 4 weeks prior to surgical resection or biopsy/catheter placement
  35. * ELIGIBILITY TO PROCEED WITH LYMPHODEPLETION
  36. * Pulmonary: Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
  37. * Cardiac: Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias
  38. * Active infection: Research participant does not have a fever exceeding 38.5 degree celsius; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to CAR T cell infusion and/or there aren't any indications of meningitis
  39. * Hepatic: Research participant serum total bilirubin or transaminases does not exceed 2 x normal limit
  40. * Renal: Research participant serum creatinine \< 1.8 mg/dL
  41. * Neurologic: Research participant does not have uncontrolled seizure activity following surgery prior to starting lymphodepletion
  42. * ELIGIBILITY TO PROCEED WITH EACH CAR T CELL INFUSION
  43. * Research participant has a released cryopreserved T cell product
  44. * Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
  45. * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias
  46. * Research participant does not have a fever exceeding 38.5 degree celsius; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis
  47. * Research participant serum total bilirubin or transaminases does not exceed 2 x normal limit
  48. * Research participant serum creatinine \< 1.8 mg/dL
  49. * Research participant does not have uncontrolled seizure activity
  50. * Research participant platelet count must be \>= 50,000. However, if platelet level is between 25,000-49,000, then T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is \>= 50,000
  51. * Research participants must not require more than 0.1mg/kg/day total dose (0.03mg/kg/dose three times per day, max of 6mg/day) of dexamethasone during CAR T cell therapy
  52. * Wash-out requirements:
  53. * At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen;
  54. * At least 23 days since the completion of temozolomide and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen. If a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose
  55. * For bevacizumab the wash out period of at least 4 weeks is required before starting study treatment
  1. * Pulmonary: Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
  2. * Cardiac: Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
  3. * Renal: Research participant requires dialysis
  4. * Neurologic: Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
  5. * Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study. A legal guardian may substitute for the research participant
  6. * Research participant with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the study team deems it unwise to enter the research participant on protocol shall be ineligible
  7. * Research participant with any other active malignancies
  8. * Research participant being treated for severe infection or recovering from major surgery is ineligible until recovery is deemed complete by the study team
  9. * Research participant with any uncontrolled illness including ongoing or active infection. Research participant with known active hepatitis B or C infection; research participant with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
  10. * Research participant who has confirmed HIV positivity within 4 weeks of enrollment
  11. * Females only: Pregnant or breastfeeding
  12. * 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)

Contacts and Locations

Principal Investigator

Leo D Wang
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Leo D Wang, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-04
Study Completion Date2025-08-24

Study Record Updates

Study Start Date2020-12-04
Study Completion Date2025-08-24

Terms related to this study

Additional Relevant MeSH Terms

  • Malignant Brain Neoplasm
  • Recurrent Malignant Brain Neoplasm
  • Refractory Malignant Brain Neoplasm