Clinical trial NCT03347097: Adoptive Cell Therapy of Autologous TIL and PD1-TIL Cells for Patients With Glioblastoma Multiforme
Official title: The Safety and Efficacy Study of Autologous Tumor-infiltrating T Lymphocyte（TIL）and Transgenic Modified TIL Cells Adoptive Therapies for Patients With Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Glioblastoma Multiforme
Keywords: glioma
TIL
PD1-TIL
immunotherapy
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Cell Therapy Research Institute
First posted: 2017-11-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: At present, the investigators want to evaluate safety and efficacy of cell therapy based on Tumor-infiltrating T Lymphocyte (TIL）in glioblastoma. Here, we also constructed a transgenic modified TIL cells, stablely express a high-level full-length PD1 antibody (PD1-TIL cells), which can transduce signals to activate T cells and result in tumor killing. In this study, we design two group patients treated with TIL cells and PD1-TIL cells respectively to determine the safety and efficacy of autologous TILs or genetically modified TILs in patients with glioblastoma.


Eligibility criteria: Inclusion Criteria:

1. Recurrent patients with histologically confirmed brain glioblastoma multiforme.
2. Patients with maximum safe resection of the tumor (≥95%) confirmed with contrast MR or CT within 72 hours after surgery.
3. Age from 18 to 70 years.
4. Karnofsky performance score ≥ 60.
5. Adequate organ function within 14 days of study registration including the following: Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count, (ANC) ≥ 1.0×10\^9/L, platelets ≥100×10\^9/L; hemoglobin ≥ 9 g/dL. Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) \< 3×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance \>60 ml/min/1.73 m2. Electrocardiogram: normal.
6. Written informed consent must be obtained from all patients.

Exclusion Criteria:

1. Pregnant or breast-feeding patients. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.

   Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
2. Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
3. Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).

Patients currently received any other investigational agents.

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Primary outcomes:
measure: Number of Adverse Events related to TIL and PD1-TIL cells infusion
timeFrame: 1 month
Secondary outcomes:
measure: Treatment Responses Rate
timeFrame: 6 months
measure: Overall Survival Rate
timeFrame: 24 months
measure: Progression-free Survival Rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan hospital, Fudan University
state: Shanghai
Study officials:
References: