Treatment of Advanced Solid Tumor With TSA-CTL(Tumor Specific Antigen-Induced Cytotoxic T Lymphocytes)
Study Details
Study Description
Brief Summary
The primary purpose of this study is to evaluate the safety of TSA-CTL in the treatment of the advanced melanoma.
The secondary purpose of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of the advanced melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is a Phase 1 clinical trial comprised of two parts. In part one, 9 subjects are assigned to group A,B,C. Dose escalation is used in In group A with no non-myeloablative chemotherapy, group B and group C will undergo a non-myeloablative chemotherapy before the cell infusion. Whether the part 2 of the trial continue is determined by the result of part
- If continues, 15 subjects will be enrolled into the trial and receive a regimen of immune cell infusion combined with non-myeloablative chemotherapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: medium dose of preparative regimen Patients will receive medium dose of lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
Biological: TSA-CTL
On day 0,TSA-CTL will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide 500 mg/m2/day IV in 250 ml for one day.
Other Names:
Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 2 days.
Other Names:
|
| Experimental: low dose of preparative regimen Patients will receive low dose of lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
Biological: TSA-CTL
On day 0,TSA-CTL will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Other Names:
Drug: Cyclophosphamide
Cyclophosphamide 500 mg/m2/day IV in 250 ml for one day.
Other Names:
Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 2 days.
Other Names:
|
| Experimental: no preparative regimen Patients will only receive TSA-CTL. |
Biological: TSA-CTL
On day 0,TSA-CTL will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [one month]
Keep records the adverse events experienced by subjects in 30 days after the first infusion.
Secondary Outcome Measures
- Disease Control Rate(DCR) [one year]
DCR is defined as the proportion of patients with tumor size reduction(CR,PR) and stable (SD) assessed by RECIST 1.1 and iRECIST.
- overall survival(OS) [one year]
The time from the first injection of Investigational Product until death.
- progression-free survival(PFS) [one year]
PFS is defined as the time from the first injection of Investigational Product until objective tumor progression or death, whichever occurs first.Assessed by RECIST 1.1 and iRECIST
- Duration of Response(DOR) [one year]
DOR refers to the period from the first evaluation of tumor as CR or PR to the first evaluation as PD(Progressive Disease) per RECIST1.1 and iRECIST.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Greater than or equal to 18 years of age and less than or equal to 70 years of age；all genders.
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Advanced solid tumors, including, but not limited to, some high-frequency somatic mutations, such as melanoma, colorectal cancer, gastric cancer, esophageal cancer, squamous cell carcinoma of the lung, three-negative breast cancer, etc.
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Advanced solid tumors patient who is HLA - A0201 /A1101/A2402 subtypes.
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Measurable metastatic melanoma with at least one lesion that is resectable or tumor biopsies for DNA extraction.
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Patient failed or be intolerant in conventional treatment.
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Able to understand and sign the Informed Consent Document.Willing to sign a durable power of attorney.
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Clinical performance status of ECOG 0 or 1 and Life expectancy of greater than six months；able to cooperate to observe adverse reactions and the effect of the treatment.
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Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to twelve months after treatment.
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Serology：Seronegative for HIV antibody，Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.Hematology：Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim，WBC greater than or equal to 3000/mm(3)，lymphocyte count greater than or equal to 800/mm(3)，Platelet count greater than or equal to 100,000/mm(3)，Hemoglobin > 9.0 g/dl Chemistry：Serum ALT/AST less than or equal to 2.5 times the upper limit of normal，Serum Creatinine less than or equal to 1.6 mg/dl，Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
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More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
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Eight weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-PD1 antibody and anti-CTLA4 antibody therapy, so at the time the patient receives the preparative regimen to allow antibody levels to decline.
Exclusion Criteria:
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Women of child-bearing potential who are pregnant or breastfeeding.
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Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
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Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
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The medical history of autoimmune disease.
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Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
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Concurrent systemic steroid therapy(in 4 weeks).
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History of severe immediate hypersensitivity reaction to any of the agents used in this study.
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Patients with unstable brain metastases.
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The choroid melanoma and clear cell sarcoma patients.
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Negative for expression of MHC molecules.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-Sen University Cancer Center | Guangzhou | Guangdong | China | 510030 |
Sponsors and Collaborators
- BGI, China
- Sun Yat-sen University
Investigators
- Principal Investigator: Xiao Sh Zhang, Doctor, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGI-001
- 2016-FXY-040
- B2016-039