Trial Title:
Safety and Efficacy of an Autologous Tumor Infiltrating Lymphocyte (TIL) Therapy in Patients with Advanced Solid Tumors
NCT ID:
NCT05831033
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Cell Therapy
Autologous Adoptive Cell Therapy
Tumor Infiltrating Lymphocytes
Study type:
Interventional
Study phase:
Early Phase 1
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:
BEN101
Description:
Lymphodepletion regimen：Cyclophosphamide 250mg/ m2/day x 3 days (day -4, -3，-2) ,
Fludarabine 25mg/ m2/day x 2 days (day-4, -3) , Paclitaxel 100mg/ m2/day -3. The
lymphodepletion regimen could be adjusted by the treating physician according to
patient's disease condition.
BEN101 infusion： Single dose level between 1x10^9 to 1x 10^11，not lower than 1×10^9
cells, final dose is affected by the starting amount of TILs cells isolated from the
tumor tissue sample.
IL-2：Administer 8-16 hr after TIL infusion. 600,000 IU/kg intravenously over 15-20 mins
every 12 hours. It is recommended to start with high dose; and de-escalate based on
tolerability, up to 5 days. IL-2 administration will be terminated if unacceptable
toxicities occur.
Arm group label:
BEN101
Summary:
Multicenter, single arm, non-randomized, prospective, open label, interventional study
evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes
(TIL) infusion (BEN101) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion
preparative regimen for the treatment of patients with recurrent and/or metastatic solid
tumor.
Detailed description:
BEN101 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing
process, for the treatment of patients with recurrent and/or metastatic solid tumor. The
cell transfer therapy used in this study involves patients receiving a NMA lymphocyte
depleting preparative regimen, followed by infusion of autologous TIL followed by the
administration of a regimen of IL-2.
Criteria for eligibility:
Criteria:
Inclusion criteria
1. Be able and willing to provide written informed consent, and to comply with all
requirements of study participation (including all study procedures).
2. Age: 18 - 75 years.
3. Histological or cytological diagnosis of advanced metastatic solid tumors.
4. Progression on standard therapy, or intolerance to, refusal or unable to benefit
from standard therapy according to investigator's judgement.
5. At least one resectable lesion (or aggregate of lesions) of a minimum 15 mm in
diameter post-resection; or core biopsy (aggregate of around 1 gram or two 18G
puncture needles).
6. At least one measurable target lesion, as defined by RECIST v1.1.Lesions in
previously irradiated areas (or other local therapy) should not be selected as
target lesions, unless treatment was ≥ 3 months prior to screening, and there has
been demonstrated disease progression in that particular lesion.
7. ECOG performance status of 0 or 1.
8. Life expectancy of at least 3 months.
9. Adequate organ and marrow function (hematology, renal, hepatic and coagulation).
1. Absolute neutrophil count (ANC) ≥ 1.0×10^9/L.
2. Hemoglobin (Hb) ≥ 80 g/L.
3. Platelet ≥ 75×10^9/L.
4. Sufficient coagulation: APPT<40 and INR<1,5.
5. Creatinine clearance (CrCL) ≥45 mL/min or serum creatinine ≤1.5mg/dL was
estimated using the Cockcroft-Gault formula.
6. Serum alanine transaminase (ALT)/ serum glutamic-pyruvic transaminase (SGPT)
and aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)
≤ 3 times the upper limit of normal (ULN); patients with liver metastasis ≤ 5
times ULN.
7. Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault
formula.
8. Total bilirubin ≤ 1.5 times ULN.
9. Patients with Gilbert's syndrome must have a total bilirubin ≤ 1.5 times
ULN.
10. Patients with left ventricular ejection fraction (LVEF) ≥50% or New York Heart
Association (NYHA) functional classification ≤ Class 1.
11. Patients with pulmonary function test (forced expiratory volume in 1 second
FEV1) ≥75%.
Exclusion criteria
1. Patients who have received an organ allograft or prior cell transfer therapy.
2. Patients who have a history of hypersensitivity to any component or excipient of
study drugs.
3. Patients who have active central nervous system (CNS) metastases（except stable brain
metastases without hormone dependence or drug treatment within 3 months before
enrollment）.
4. Patients who have active medical illness(es) that would pose increased risk for
study participation, including: active systemic infections requiring systemic
antibiotic therapy, coagulation disorders, or other active major medical illnesses
of the cardiovascular, respiratory, or immune system.
5. Active hepatitis C subjects (Hepatitis C virus (HCV) antibody positive and
peripheral blood HCV RNA positive), human immunodeficiency virus (HIV) antibody
positive; syphilis primary screening antibody positive; untreated active hepatitis B
subjects (hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody
(HBcAb) positive and peripheral blood HBV DNA quantitative test greater than ULN),
hepatitis B subjects need to receive anti-HBV treatment during the study period.
6. Previous history of immunodeficiency (any form, primary or acquired), current
long-term use of systemic corticosteroids or other immunosuppressants. Patients
receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10
mg/day of prednisone or other steroid equivalent may be eligible.
7. Patients who have had another primary malignancy within the previous 3 years (with
the exception of carcinoma in situ of the breast, cervix, or bladder; localized
prostate cancer; and non-melanoma skin cancer that has been adequately treated).
8. Patients who have received a live or attenuated vaccine within 28 days before
signing the informed consent.
9. Received other cell therapy products in the past.
10. History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where
considered drug related and cytokine release syndrome) that was considered related
to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory
agents, etc.) and required immunosuppressive therapy.
11. Patients who are pregnant or breastfeeding.
12. Before enrollment, adverse event due to any previous treatment or surgery which had
not recovered to ≤ Grade 1 (according to CTCAE V5.0); except: alopecia, peripheral
neuropathy ≤ grade 2, events that remain stable during supportive therapy (such as
stable hypothyroidism with hormone replacement therapy), or other events that have
no safety risk as assessed by the investigator.
13. Patients who do not consent to the use of medically approved contraceptive methods
during the study.
14. Patients whose cancer requires immediate attention or who in the investigator's
judgement is not suitable to participate in this trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
RenJi Hospital
Address:
City:
Shanghai
Zip:
200125
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Wenjing Wang, Master
Phone:
+86 18964874021
Email:
wenjingwang2@126.com
Contact backup:
Last name:
Wen Kong, Doctor
Phone:
+8613585982964
Email:
kongwen@renji.com
Facility:
Name:
Shanghai General Hospital
Address:
City:
Shanghai
Zip:
201620
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
weiyi Huang, Master
Phone:
+86 13817373650
Email:
huangweiyi1976@163.com
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
jianhua chen, Doctor
Phone:
+86 17321168230
Email:
jianhuachen15@163.com
Start date:
May 23, 2023
Completion date:
June 15, 2027
Lead sponsor:
Agency:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Shanghai General Hospital, Shanghai Jiaotong University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Renji Hospital, Shanghai
Agency class:
Other
Collaborator:
Agency:
Fudan University
Agency class:
Other
Source:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05831033
