Solid CancerPhase 1NCT02959905
Treatment of Advanced Solid Tumors With TSA-CTL(Tumor Specific Antigen-Induced Cytotoxic T Lymphocytes)
A Phase 1 study testing TSA-CTL, Cyclophosphamide and Fludarabine in people with Solid Cancer, run by BGI, China at 1 site in China.
Trial summary
The primary objective of this study is to evaluate the safety of TSA-CTL in the treatment of advanced solid tumors. The secondary objective of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Solid Cancer
- What is being tested?
- TSA-CTL, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteChina
- Study dates
- 22 Dec 2016to 20 May 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Greater than or equal to 18 years of age and less than or equal to 70 years of age; all genders.
- 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, triple-negative breast cancer, etc.
- Advanced solid tumors patients who are HLA - A0201 /A1101/A2402 subtypes.
- Measurable solid tumors with at least one lesion that is resectable or tumor biopsies for DNA extraction.
- Patients who failed or were intolerant to standard treatment.
- Patients (or their legal representatives) who are able to understand and sign the Informed Consent Form and willing to sign a durable power of attorney.
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- Clinical performance status of ECOG is 0 or 1 and expected lifetime is greater than six month and patients who are able to cooperate to observe adverse reactions and the effect of the treatment.
- Patients of both genders must be willing to practice birth control from the time of enrollment to five months after treatment on this study.
- Serology: HIV antibody(-), hepatitis B antigen(-), and hepatitis C antibody(-). A fertile woman must have a negative pregnancy test. Hematology: Absolute neutrophil count is greater than 1500/mm3 without the support of filgrastim; WBC is greater than or equal to 3000/mm3; lymphocyte count is greater than or equal to 800/mm3; Platelet count is greater than or equal to 100,000/mm3; Hemoglobin is greater than or equal to 9.0 g/dL ; Chemistry: Serum ALT/AST is less than or equal to 2.5 times the upper limit of normal; Serum Creatinine is less than or equal to 1.5 times the upper limit of normal ; Total bilirubin is less than or equal to 1.5 the upper limit of normal, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 times the upper limit of normal.
- More than four weeks must have elapsed since any prior systemic 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).
- 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.
Who cannot join
- Pregnant or lactating women.
- Any primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Opportunistic infection.
- History of autoimmune disease.
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
- Systemic steroid therapy in the past 4 weeks.
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- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Patients with unstable brain metastases.
- Choroidal melanoma and clear cell sarcoma patients.
- Negative for expression of MHC molecules.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Clinical Trial of TSA-CTL (Tumor Specific Antigen-Induced Cytotoxic T Lymphocytes) In the Treatment of Advanced Solid Tumors
The primary objective of this study is to evaluate the safety of TSA-CTL in the treatment of advanced solid tumors.
The secondary objective of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of advanced solid tumors.
Read the detailed description
This is a single arm, open label and non-randomized clinical study with two parts.
In Part 1, 9 subjects with advanced solid tumors will be enrolled into Groups A (no non-myeloablative lymphodepletion), B and C (non-myeloablative lymphodepletion with different chemotherapy intensities) to assess the safety and dose intensity of non-myeloablative lymphodepletion chemotherapy before cell infusion.
Depending on results in Part 1, the study may proceed to Part 2, where 15 subjects with advanced solid tumors will be enrolled to receive TSA-CTL cell infusions with or without non-myeloablative lymphodepletion.
- Conditions
- Solid Cancer
- Being tested
- TSA-CTL, Cyclophosphamide, Fludarabine
- Keywords
- Metastatic Melanoma, Colorectal Cancer, neoantigen
- Medical subject headings
- Melanoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TSA-CTLBiological
Also called Tumor Specific Antigen Induced Cytotoxic Lymphocyte
Patients will receive TSA-CTL iv over 20-30 minutes on day 0.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide 500 mg/m2/day iv on day -5 for one day.
FludarabineDrug
Also called Fludarabine Phosphate
Fludarabine 25 mg/m2/day iv over 30 minutes on day -5 and -4 for two days.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide 500 mg/m2/day iv on day -5 and -4 for two days.
| Study group | Role | What they receive |
|---|---|---|
| medium-dose lymphodepletion regimen | Experimental | Patients will receive medium-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. Receives: Biological: TSA-CTL; Drug: Fludarabine; Drug: Cyclophosphamide |
| low-dose lymphodepletion regimen | Experimental | Patients will receive low-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. Receives: Biological: TSA-CTL; Drug: Cyclophosphamide; Drug: Fludarabine |
| No lymphodepletion regimen | Experimental | Patients will only receive TSA-CTL. Receives: Biological: TSA-CTL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as assessed by CTCAE v5.0.
Keep records the adverse events experienced by subjects in 30 days after the first infusion.
Measured: one month
Secondary outcomes (4)
Disease Control Rate(DCR)
DCR is defined as the proportion of participants with tumor size reduction(CR,PR) and stable disease(SD) assessed by RECIST 1.1 and iRECIST.
Measured: one year
overall survival(OS)
The time from the first infusion of Investigational Product until death.
Measured: one year
progression-free survival(PFS)
PFS is defined as the time from the first infusion of Investigational Product until objective tumor progression, as assessed by RECIST 1.1 and iRECIST, or death, whichever occurs first.
Measured: one year
Duration of Response(DOR)
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.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study start22 Dec 2016
- Primary completion1 Sep 2020
- Study completion20 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Solid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- BGI, China
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-sen University
- Responsible party
- Sponsor
- Investigators
- Xiao Sh Zhang, Doctor, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02959905
- Sponsor's protocol ID
- BGI-001
- Other IDs
- 2016-FXY-040, B2016-039
- Status last verified
- Feb 2023
- First submitted
- 21 Oct 2016
- Last updated
- 2 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.
PubMed 24812403Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.
PubMed 25837513Prickett TD, Crystal JS, Cohen CJ, Pasetto A, Parkhurst MR, Gartner JJ, Yao X, Wang R, Gros A, Li YF, El-Gamil M, Trebska-McGowan K, Rosenberg SA, Robbins PF. Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens. Cancer Immunol Res. 2016 Aug;4(8):669-78. doi: 10.1158/2326-6066.CIR-15-0215. Epub 2016 Jun 16.
PubMed 27312342Li D, Chen C, Li J, Yue J, Ding Y, Wang H, Liang Z, Zhang L, Qiu S, Liu G, Gao Y, Huang Y, Li D, Zhang R, Liu W, Wen X, Li B, Zhang X, Zhang X, Xu RH. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors. Nat Commun. 2023 Jun 10;14(1):3447. doi: 10.1038/s41467-023-39225-7.
PubMed 37301885
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of TSA-CTL (Tumor Specific Antigen-Induced Cytotoxic T Lymphocytes) In the Treatment of Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02959905
- Acronym / sponsor ID
- BGI-001
- Conditions
- Solid Cancer
- Keywords
- Metastatic Melanoma, Colorectal Cancer, neoantigen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- BGI, ChinaUniversity, hospital or other
- Collaborators
- Sun Yat-sen University
- Study start
- 22 Dec 2016 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 20 May 2022 (actual)
- First posted
- 9 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety of TSA-CTL in the treatment of advanced solid tumors.
The secondary objective of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of advanced solid tumors.
Detailed description
This is a single arm, open label and non-randomized clinical study with two parts.
In Part 1, 9 subjects with advanced solid tumors will be enrolled into Groups A (no non-myeloablative lymphodepletion), B and C (non-myeloablative lymphodepletion with different chemotherapy intensities) to assess the safety and dose intensity of non-myeloablative lymphodepletion chemotherapy before cell infusion.
Depending on results in Part 1, the study may proceed to Part 2, where 15 subjects with advanced solid tumors will be enrolled to receive TSA-CTL cell infusions with or without non-myeloablative lymphodepletion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| medium-dose lymphodepletion regimen | Experimental | Biological: TSA-CTL, Drug: Fludarabine, Drug: CyclophosphamidePatients will receive medium-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
| low-dose lymphodepletion regimen | Experimental | Biological: TSA-CTL, Drug: Cyclophosphamide, Drug: FludarabinePatients will receive low-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
| No lymphodepletion regimen | Experimental | Biological: TSA-CTLPatients will only receive TSA-CTL. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Greater than or equal to 18 years of age and less than or equal to 70 years of age; all genders.
- 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, triple-negative breast cancer, etc.
- Advanced solid tumors patients who are HLA - A0201 /A1101/A2402 subtypes.
- Measurable solid tumors with at least one lesion that is resectable or tumor biopsies for DNA extraction.
- Patients who failed or were intolerant to standard treatment.
Key exclusion criteria (10 listed)
- Pregnant or lactating women.
- Any primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Opportunistic infection.
- History of autoimmune disease.
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TSA-CTLAlso: Tumor Specific Antigen Induced Cytotoxic LymphocytePatients will receive TSA-CTL iv over 20-30 minutes on day 0. | Biological | No lymphodepletion regimen, low-dose lymphodepletion regimen, medium-dose lymphodepletion regimen |
| CyclophosphamideAlso: CytoxanCyclophosphamide 500 mg/m2/day iv on day -5 for one day. | Drug | low-dose lymphodepletion regimen |
| FludarabineAlso: Fludarabine PhosphateFludarabine 25 mg/m2/day iv over 30 minutes on day -5 and -4 for two days. | Drug | low-dose lymphodepletion regimen, medium-dose lymphodepletion regimen |
| CyclophosphamideAlso: CytoxanCyclophosphamide 500 mg/m2/day iv on day -5 and -4 for two days. | Drug | medium-dose lymphodepletion regimen |
Primary outcome
Number of participants with adverse events as assessed by CTCAE v5.0.
Time frame: one month
Keep records the adverse events experienced by subjects in 30 days after the first infusion.
4 secondary outcomes
Disease Control Rate(DCR)
Time frame: one year
overall survival(OS)
Time frame: one year
progression-free survival(PFS)
Time frame: one year
Duration of Response(DOR)
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
- Results publication: PubMed 24812403Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.
- Results publication: PubMed 25837513Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.
- Results publication: PubMed 27312342Prickett TD, Crystal JS, Cohen CJ, Pasetto A, Parkhurst MR, Gartner JJ, Yao X, Wang R, Gros A, Li YF, El-Gamil M, Trebska-McGowan K, Rosenberg SA, Robbins PF. Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens. Cancer Immunol Res. 2016 Aug;4(8):669-78. doi: 10.1158/2326-6066.CIR-15-0215. Epub 2016 Jun 16.
- Derived from this study: PubMed 37301885Li D, Chen C, Li J, Yue J, Ding Y, Wang H, Liang Z, Zhang L, Qiu S, Liu G, Gao Y, Huang Y, Li D, Zhang R, Liu W, Wen X, Li B, Zhang X, Zhang X, Xu RH. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors. Nat Commun. 2023 Jun 10;14(1):3447. doi: 10.1038/s41467-023-39225-7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiao Sh Zhang, Doctor principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TSA-CTL, Cyclophosphamide and Fludarabine in people with Solid Cancer, run by BGI, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events as assessed by CTCAE v5.0. (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02959905, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2023.