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

NCT04510051 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 19130NCI-2020-05158P30CA033572
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Malignant Brain Neoplasm; Recurrent Malignant Brain Neoplasm; Refractory Malignant Brain Neoplasm

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will assess the incidence of grade 3 toxicities, dose limiting toxicities, and all other toxicities. Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and the revised cytokine release syndrome (CRS) grading system. Symptoms and toxicities will be evaluated by physical exam and blood chemistry/hematology results and adverse event reporting. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants experiencing dose limiting toxicities. Tables will be created to summarize all toxicities and side effects by time post treatment, organ, severity and disease subgroup.

  Up to 1 year after the last chimeric antigen response (CAR) T cell infusion

Secondary Outcomes (9)

• Persistence and expansion of CAR T cells

  Up to 1 year after the last CAR T cell infusion

• Peripheral blood and CSF cytokine levels

  Up to 1 year after the last CAR T cell infusion

• Peripheral blood and CSF immune cell characterization

  Up to 1 year after the last CAR T cell infusion

• Progression free survival

  From time of lymphodepletion to the event date (progressionor death), assessed at 6 months

• Overall survival

  From time of lymphodepletion to date of death, assessed at 1 year after the last CAR T cell infusion

Study Arms (1)

Treatment (chemotherapy, IL13(EQ)BBzeta/CD19t+ T cells)

EXPERIMENTAL

Patients receive cyclophosphamide intravenously IV on days -5 and -4, and fludarabine IV on days -5 to -2. Patients then receive autologous IL13(EQ)BBzeta/CD19t+ T cells intraventricularly over 5 minutes QW on day 0. Treatment with autologous IL13(EQ)BBzeta/CD19t+ T cells repeats every 7 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of IL13(EQ)BBzeta/CD19t+ T cells as long as they continue to meet eligibility criteria and have doses available for infusion.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (chemotherapy, IL13(EQ)BBzeta/CD19t+ T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (chemotherapy, IL13(EQ)BBzeta/CD19t+ T cells)

IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes BIOLOGICAL

Given intraventricularly

Also known as: Autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T Cells

Treatment (chemotherapy, IL13(EQ)BBzeta/CD19t+ T cells)

Eligibility Criteria

• Age: 4 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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
• 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
• Life expectancy \> 4 weeks
• Participant has a prior histologically-confirmed malignant brain neoplasm and has progressed after prior conventional therapy
• 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)
• City of Hope (COH) clinical pathology confirms IL13Ralpha2+ tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50)
• 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
• Platelets \>= 50,000/mm\^3 (performed within 6 weeks of signing the main informed consent)
• Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 6 weeks of signing the main informed consent)
• Aspartate transaminase (AST) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent)
• Alanine transferase (ALT) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent)
• Creatinine clearance of \>= 75mL/min/1.73m\^2 (performed within 6 weeks of signing the main informed consent)
• 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)

You may not qualify if:

• Pulmonary: Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
• Cardiac: Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
• Renal: Research participant requires dialysis
• Neurologic: Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• 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
• 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
• Research participant with any other active malignancies
• Research participant being treated for severe infection or recovering from major surgery is ineligible until recovery is deemed complete by the study team
• 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
• Research participant who has confirmed HIV positivity within 4 weeks of enrollment
• Females only: Pregnant or breastfeeding
• 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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

C.S. Mott Children's Hospital, University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Leo D Wang

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: August 12, 2020
• Study Start: December 4, 2020
• Primary Completion (Estimated): February 24, 2027
• Study Completion (Estimated): February 24, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (3)