Clinical trial NCT03423992: Personalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas
Official title: A Pilot Study to Evaluate the Safety and Efficacy of Personalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas Based on the Expression of Tumor Specific/Associated Antigens
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Glioma
Malignant Glioma of Brain
Recurrence Tumor
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Beijing Mario Biotech Company
name: Hebei Senlang BIotech Company
name: Beijing HuiNengAn Biotech Company
First posted: 2018-02-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A pilot study to determine the safety and efficacy of chimeric antigen receptor T cell (autologous T cells transduced with a lentiviral vector expressing chimeric antigen receptor with or without anti-PDL1 antibody) personalized immunotherapy for patients with recurrent malignant gliomas based on the expression of tumor specific/associated antigens (EGFRVIII, IL13Rα2, Her-2, EphA2, CD133, GD2).


Eligibility criteria: Inclusion Criteria:

* Voluntary informed consent for entry of trial;
* Age greater than 18 years, and less than 70 years;
* Pathologically confirmed recurrent malignant gliomas;
* Tumor cells from resected tissue must be available for antigen testing (EGFRvIII, IL13Rα2, Her-2, CD133, EphA2, GD2) and at least one of the targets should be tested positively by immunohistochemistry study;
* If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.
* Patients must have a Karnofsky performance status of greater than or equal to 70.
* Life expectancy greater than 3 months;
* Participants with adequate organ function as measured by:

  1. White blood count greater than or equal to 2500/mm\^3; platelets greater than or equal to 100,000/mm\^3, hemoglobin greater than or equal to 10.0 g/dL; without transfusion or growth factor support
  2. Aspartate transaminase (AST), Alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT), lactic acid dehydrogenase (LDH), alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
  3. Serum creatinine less than or equal to 1.5 x upper limit of normal
  4. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.

Exclusion Criteria:

* Female subjects of reproductive potential who are pregnant or lactating;
* Previous treatment with any gene therapy products or other form immunotherapy;
* Uncontrolled active infection.
* Active or latent chronic hepatitis B \[detectable hepatitis B surface antigen (HBsAg)\] or active hepatitis C (positive serology \[hepatitis C virus Ab\]) infection.
* HIV infection;
* History of allergy or hypersensitivity to study product excipients (human serum albumin, Dimethyl sulfoxide, and Dextran 40);
* Currently enrolled in other clinical trials;

Primary outcomes:
measure: Adverse events attributed to the administration of the chimeric antigen receptor T cells
timeFrame: 1 year
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 1 year
measure: clinical activity of chimeric antigen receptor T cells
timeFrame: 28 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital
Study officials:
References:
citation: Lin Q, Ba T, Ho J, Chen D, Cheng Y, Wang L, Xu G, Xu L, Zhou Y, Wei Y, Li J, Ling F. First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose. Front Oncol. 2021 Jun 21;11:694941. doi: 10.3389/fonc.2021.694941. eCollection 2021.