Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Recurrence

Brain Neoplasms

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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

Leo D. Wang

Leo D Wang

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.

PRIMARY OBJECTIVE:

I. To assess the feasibility and safety of lymphodepleting chemotherapy followed by cellular immunotherapy utilizing IL13Ralpha2-specific hinge-optimized 41BB-co-stimulatory chimeric antigen receptor \[CAR\] truncated CD19-expressing autologous T-lymphocytes (IL13\[EQ\]BBzeta/CD19t+ Tn/mem cells) administered by intraventricular (ICV) delivery for pediatric participants with IL13Ralpha2+ recurrent/refractory brain tumors.

SECONDARY OBJECTIVES:

I. To describe persistence and expansion of CAR T cells in peripheral blood (PB) and cerebrospinal (CSF).

II. To describe cytokine levels (PB, and CSF) over the study period.

III. In research participants who receive the full schedule of 4 CAR T cell cycles:

IIIa. To estimate 6-month progression free survival (PFS) rate per disease. IIIb. To estimate disease response rates per disease. IIIc. To estimate 1-year overall survival rate per disease. IV. To evaluate the use of circulating tumor deoxyribonucleic acid (ctDNA) to evaluate tumor burden.

V. For study participants who undergo an additional biopsy/resection or autopsy:

Va. To evaluate CAR T cell persistence in the tumor tissue and the location of the CAR T cells with respect to the infusion site. Vb. To evaluate IL13Ralpha2 antigen expression levels on tumor tissue pre and post CAR T cell therapy.

OUTLINE: This is a dose-escalation study of IL13(EQ)BBzeta/CD19t+ T cells.

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 once a week (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.

After completion of study treatment, patients are followed for up at 30 days, 3, 6, 9, and 12 months, and then yearly for 15 years.

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

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

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.

Will assess CAR T cells detected in peripheral blood and cerebrospinal fluid (CSF). Descriptive statistical and graphical methods will be used to describe persistence and expansion of the CAR T cells (peripheral blood \[PB\] and CSF).

Descriptive statistical and graphical methods will be used to describe cytokine levels (PB and CSF).

Will estimate the rate (90% confidence interval \[CI\]) of disease response Disease status will be assessed by the grading of the tumor responses performed according to the Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

Descriptive statistical and graphical methods will be used to describe ctDNA.

Spots Global Cancer Trial Database for recurrent malignant brain neoplasm