Adoptive Cell Therapy of Autologous TIL and PD1-TIL Cells for Patients With Glioblastoma Multiforme

Early Phase 1

• Conditions: Glioblastoma Multiforme
• Interventions: Drug: TIL; Drug: PD1-TIL

• Registration Number: NCT03347097
• Lead Sponsor: Huashan Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-01
• Study First Submitted: 2017-11-02
• Study First Submitted QC: 2017-11-16
• Study First Posted: 2017-11-20
• Primary Completion: 2020-01-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-24
• Last Update Posted: 2021-08-25
• Study Completion: 2021-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TIL cells	TIL	10 days after the end of chemotherapy or radiotherapy，the 300ml TIL cells ( TIL saline + 0.25% human serum albumin) was injected intravenously 2 times every 30 days .
PD1-TIL cells	PD1-TIL	10 days after the end of chemotherapy or radiotherapy，the 300ml PD1-TIL cells ( PD1-TIL saline + 0.25% human serum albumin) was injected intravenously 2 times every 30 days .

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events related to TIL and PD1-TIL cells infusion	1 month

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival Rate	12 months
Treatment Responses Rate	6 months
Overall Survival Rate	24 months

Trial Locations

Locations (1)

Huashan hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China