Solid Tumor
Conditions
Keywords
HPV-16 Positive, Adoptive T Cell Therapy, Recurrent or Metastatic Cervical Cancer, HPV-T
Brief summary
The purpose of this protocol is to evaluate the feasibility and safety of HPV-T in HPV 16 positive recurrent or metastatic solid tumor patients.
Detailed description
In this study, HPV-T cells will be cultured from mononuclear cells collected from participant's peripheral blood in the laboratory and they will be given back to the participant intravenously. The use of HPV-T cells involves a combination of IL-2, which is a drug used to help the body's response to treatment on the immune system. A medium dose regimen of IL-2 will be given after the participant receives the infusion of the T-cells. Each HPV-T cell reinfusion is a treatment cycle, and each participant will receive a maximum of four cycles of HPV-T treatment. Whether the participant receives the next cycle of treatment depends on the efficacy of the previous HPV-T treatment, which is assessed by imaging.
Interventions
BIOLOGICALHPV-T
Participant will receive HPV-T iv on day 0. One time of cell infusion constitute a cycle, each participant receives up to four cycles of treatment
DRUGInterleukin-2
500,000IU/m\^2 SC, after each cell infusion, IL-2 will start within 24 hours and every 8-12 hours for up to 6 doses.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
BGI, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 years of age and less than or equal to 75 years of age; all genders. 2. Confirmed diagnosis of recurrent of metastatic solid tumor and at least one measurable lesion. 3. HLA type is HLA-A0201. 4. HPV 16 positive. 5. Patients who failed or were intolerant to standard first-line treatment. 6. Possess venous access for mononuclear cell collection or intravenous blood collection. 7. Clinical performance status of ECOG is 0 or 1. 8. Possess venous access for mononuclear cell collection or intravenous blood collection. 9. Patients who are able to cooperate to observe adverse reactions and the effect of the treatment,expected lifetime is greater than six month. 10. Patients of both genders must be willing to practice birth control from the time of enrollment to three months after treatment on this study,a fertile woman must have a negative pregnancy test. 11. The laboratory test values and the functions of important organs meet the following requirements: 1#Serology: HIV antibody(-), hepatitis B DNA(-), hepatitis C antibody(-) and no active syphilis infection; 2#Hematology: Absolute neutrophil count is greater than or equal to 1.5×10\^9/L; WBC is greater than or equal to 3×10\^9/L; lymphocyte count is greater than or equal to 0.8×10\^9/L; Platelet count is greater than or equal to 100×10\^9/L; Hemoglobin is greater than or equal to 85g/L ; 3#Chemistry: Serum ALT/AST is less than or equal to 3 times ULN,except in patients with liver metastasis who must have ALT/AST less than or equal to 5 times ULN; Serum Creatinine is less than or equal to 1.5 times ULN ; Total bilirubin is less than or equal to 1.5 times ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 times ULN; 4#Blood Clotting Parameters:Prothrombin Time(PT) and International Normalised Ratio (INR) are less than or equal to 1.5 times ULN;Activated Partial Thromboplastin Time (APTT) is less than or equal to 1.5 times ULN;For subjects who frequently take anticoagulant drugs,their blood clotting parameters can meet the value range adoptive to this special population; 5#Left ventricular ejection fraction#LVEF#is more than or equal to 50%. 12. More than four weeks must have elapsed since any prior systemic therapy (except for bridging therapy) at the time the patient receives the lymphodepletion regimen, and toxicities must have recovered to grade 1 or less (except for toxicities such as alopecia or vitiligo)
Exclusion criteria
1. Pregnant or lactating women. 2. History of severe immediate hypersensitivity reaction to HPV-T and any of the agents used in this study. 3. Participants with a history of organ transplantation. 4. Participants with brain metastases. 5. Any active autoimmune disease or participants with a history of autoimmune diseases that have been assessed by the investigator to be unsuitable for this study. Including but not limited to the following diseases: such as systemic lupus erythematosus, immune related neuropathy, multiple sclerosis, Guillain Barre syndrome, myasthenia gravis, connective tissue diseases, inflammatory bowel diseases(Crohn's disease and ulcerative colitis), excluding vitiligo, eczema, type I diabetes, rheumatoid arthritis and other joint diseases, Sjogren's syndrome and controlled psoriasis by local medication. 6. Active systemic infections, for example, acute infections requiring systemic antibiotic, antiviral, or antifungal treatment occur within 2 weeks before enrollment. 7. Severe liver and kidney function damage(given treatment is still uncontrollable, and biochemical indicators cannot meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events as assessed by CTCAE v5.0 | Up to 24 months | Toxicity will be assessed within 4 weeks of the HPV-T transfer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response | Up to 24 months | Participants displaying objective response associated with the treatment regimen per Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Disease control rate (DCR), Duration of Response (DOR), Overall Survival(OS) and Progression-free survival (PFS) will be also evaluated. |
Countries
China
Contacts
Primary ContactGuiling Li, Doctor
Outcome results
None listed