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

The Safety and Efficacy Study of Autologous Tumor-infiltrating T Lymphocyte（TIL）and Transgenic Modified TIL Cells Adoptive Therapies for Patients With Glioblastoma Multiforme

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: TIL; Drug: PD1-TIL

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TIL cells; 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 .	Drug: TIL
EXPERIMENTAL: PD1-TIL cells; 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 .	Drug: PD1-TIL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events related to TIL and PD1-TIL cells infusion	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment Responses Rate	6 months
Overall Survival Rate	24 months
Progression-free Survival Rate	12 months

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai Cell Therapy Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2017
• Primary Completion (ACTUAL): January 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (ACTUAL): November 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; glioma; TIL; PD1-TIL
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: KY2017-241

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No