Trial Title:
TIL Therapy Combined With Pembrolizumab for Advanced Brain Cancer Including Gliomas and Meningiomas
NCT ID:
NCT06640582
Condition:
Brain Tumor
Brain Metastases
Brain Cancer
Glioma
Gliomas, Malignant
Glioblastoma
Meningioma
Conditions: Official terms:
Glioblastoma
Glioma
Brain Neoplasms
Meningioma
Cyclophosphamide
Pembrolizumab
Fludarabine
Interleukin-2
Conditions: Keywords:
Tumor Infiltrating Lymphocytes
CAR-T CELL
Biological Therapy
Advanced or Metastatic Refractory
Immunotherapy
TIL
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Tumor Infiltrating Lymphocytes (TIL)
Description:
Tumor Infiltrating Lymphocytes (TIL) IV
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine will be administered as an intravenous (IV) infusion for five days.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Interleukin-2
Description:
After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for
a maximum of eight doses.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Intravenous (IV) infusion
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Summary:
This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating
lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in
patients with Advanced Brain Cancer including Gliomas and Meningiomas . Lifileucel
(Amtagvi), the first FDA-approved TIL therapy, has demonstrated significant success in
treating unresectable or metastatic melanoma by utilizing the patient's own immune cells
to combat cancer. This study aims to apply a similar approach to Brain cancer. TILs will
be harvested from patients' tumors, expanded in vitro, and infused back into the patients
following a non-myeloablative lymphodepletion regimen. Pembrolizumab, a monoclonal
antibody targeting the PD-1 receptor on T cells, will be administered to enhance the
immune response. The primary endpoint is to determine the objective response rate (ORR)
of this combined therapy. Secondary endpoints include disease control rate (DCR),
progression-free survival (PFS), overall survival (OS), duration of response (DOR), and
quality of life (QoL). This trial aims to offer a novel, personalized treatment option
for patients with limited therapeutic alternatives.
Detailed description:
Tumor-infiltrating lymphocytes (TILs) therapy is an innovative form of adoptive cell
therapy that utilizes the patient's own immune cells to target and destroy cancer cells.
Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has shown remarkable efficacy
in treating unresectable or metastatic melanoma. By extracting lymphocytes from the
patient's tumor, expanding them ex vivo, and reinfusing them, Lifileucel has
significantly improved the immune system's ability to combat cancer cells. This promising
approach forms the basis for this study, which aims to apply similar methodologies to
advanced or metastatic refractory lung cancer, a condition that generally has a poor
prognosis and limited treatment options.
This trial involves several steps: initially, tumor samples are collected from patients
for TIL extraction. Afterward, a lymphodepletion regimen using cyclophosphamide and
fludarabine is administered to prepare the body for the infusion of expanded autologous
TILs. Following the TIL infusion, Aldesleukin (IL-2) is administered to stimulate the
TILs' activity. Pembrolizumab (Keytruda), an immunotherapy targeting the PD-1 receptor on
T cells, is also given to further enhance the immune response against the tumor.
The primary goal of this trial is to determine the objective response rate (ORR) of this
combined therapy. Secondary endpoints include the disease control rate (DCR),
progression-free survival (PFS), overall survival (OS), duration of response (DOR), and
changes in the quality of life (QoL) of patients.
Patients will be closely monitored for side effects and reactions during their hospital
stay and throughout the follow-up period. Safety will be assessed based on the incidence
and severity of adverse events, while efficacy will be evaluated using RECIST v1.1
criteria. By leveraging the patient's own immune cells and combining them with advanced
immunotherapies, this trial aims to provide a novel, personalized treatment option for
patients with advanced or metastatic refractory lung cancer, building on the success
observed with Lifileucel (Amtagvi) in melanoma treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age: 16 years to 90 years
- Histologically diagnosed as primary/relapsed/metastasized brain glioma
- Expected life span more than 3 months
- Karnofsky≥60% or ECOG score 0-2
- Test subjects have failed standard treatment regimens, or there are no standard
treatment regimens available.
- Test subjects must have tumor regions eligible for biopsy or resection, or malignant
body fluid where TILs can be isolated
- At least 1 evaluable tumor lesion
- Hematology and Chemistry（within 7 days prior to enrollment）:
- Absolute count of white blood cells≥2.5×10^9/L
- Absolute count of neutropils≥1.5×10^9/L
- Absolute count of lymphocytes ≥0.7×109/L
- Platelet count≥100×10^9
- hemoglobin≥90 g/L
- Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant
therapy within the previous 3 days)
- International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy
within the previous 3 days)
- Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min
- Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN)
- Totol bilirubin≤1.5×ULN
- No absolute or relative contraindications to operation or biopsy
- Test subjects with child-bearing potential must be willing to practice approved
highly effective methods of contraception at the time of informed consent and
continue within 1 year after the completion of lymphodepletion
- Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, and
biologics must cease 28 days before obtaining TILs
- Be able to understand and sign the informed consent document;
- Be able to stick to follow-up visit plan and other requirements in the agreement.
Exclusion Criteria:
- Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or
equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory
treatment
- Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of
the lung for carbon monoxide (DLCO) (calibrated) less than 40%
- Significant cardiovascular anomalies according to any of the following definitions:
- New York Heart Association (NYHA) Grade III or IV congestive heart failure,
clinically significant
- Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection
fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as
ventricular arrhythmia requiring clinical intervention, second-third degree
atrioventricular conductive block, etc.
- Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active
HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection
or Treponema pallidum antibody positive.
- Severe physical or mental diseases;
- Have a systemic active infection requiring treatment, or have positive blood
cultures(or imaging evidence of infection).
- Having been treated within a month or being treated now with other medicines, or
other biologic therapy, chemo-or radiotherapy.
- History of allergy to chemical compounds consisting of chemical and biological
substances resembling cell therapy.
- Having received immunotherapy and developed an irAE level greater than Level 3.
- Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below
(toxicity considered by the investigator as non-safety concerns like alopecia
excluded).
- Females in pregnancy or lactation. History of organ transplantation, allogeneic stem
cell transplantation, and renal replacement therapy.
- Researchers consider the test subject as having a history of other severe systemic
diseases, or other reasons inappropriate for the clinical study.
Gender:
All
Minimum age:
16 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
District One Hospital
Address:
City:
Beijing
Zip:
086-373
Country:
China
Status:
Recruiting
Contact:
Last name:
SAMI XI, dr
Phone:
+14012275001
Email:
SFM@districtonehospital.com
Start date:
October 20, 2024
Completion date:
December 28, 2026
Lead sponsor:
Agency:
Essen Biotech
Agency class:
Other
Source:
Essen Biotech
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06640582
