Recurrence TumorPhase 1/2NCT03658785
Immunotherapy for the Treatment of Advanced Solid Tumor
A Phase 1/2 study testing TIL, Aldesleukin and Cyclophosphamide in people with Recurrence Tumor and Metastatic Cancer, run by Tongji Hospital at 1 site in China.
Trial summary
The purpose of this study is to evaluate the safety, side effects and benefits of autologous tumor infiltrating lymphocytes (TIL) specific to personalized Neo-antigens in the treatment of patients with recurrent, metastatic and advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Recurrence Tumor, Metastatic Cancer, Solid Tumor
- What is being tested?
- TIL, Aldesleukin and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 28 Apr 2020to 31 Dec 2025
- Phase
- Phase 1/2
- 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
- To be eligible for the study, patients must meet ALL of the following criteria prior to enrollment in the study:
- Must be ≥ 18 years of age at the time of consent.
- Must have recurrent, metastatic, or persistent carcinoma that is not amenable to curative treatment with surgery and/or radiation therapy and for which no other therapies are expected to have significant benefit, in the opinion of the Investigator.
- Must have at least 1 lesion that is resectable for TIL generation. The resected TIL generating lesion(s) should yield at least 1.5 cm in diameter post-resection of tumor tissue. Following resection for TIL generation, must have a remaining measurable target lesion as defined by RECIST v1.1.
- Patients must have progressive disease while receiving or after the completion of the most recent prior treatment.
- Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to tumor resection. Radiation therapy may have been received up to 28 days prior to tumor resection for lesions not expected to be used for TIL generation or target lesions.
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- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Patients must be seronegative for the human immunodeficiency virus (HIV).
- Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment.
- Hematology:
- Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim;White blood cell (WBC) greater than or equal to 3000/mm(3);Platelet count greater than or equal too 100,000/mm(3);Hemoglobin greater than 8.0 g/dl.
- Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to to 2.5 times the upper limit of normal. Serum creatinine less than or equal to to 1.6 mg/dl.Total bilirubin less that 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.
- Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
Who cannot join
- Patients who have received an organ allograft or prior cell transfer therapy.
- Patients who are on a systemic steroid therapy > 10 mg of prednisone daily or other steroid equivalent.
- Patients who currently have prior therapy-related toxicities greater than Grade 1 according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment/resection.
- Patients who have a contraindication to or history of hypersensitivity reaction to any component or excipients of the TIL therapy and the other study drugs.
- Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory, or immune system.
- Patients with symptomatic and/or untreated brain metastases (of any size and any number).
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- Patients who have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
- Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis.
- Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher.
- Patients who have a forced expiratory volume in 1 second (FEV1) of less than or equal to 60% of predicted normal.
- Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen.
- Patients whose cancer requires immediate treatment or who would otherwise suffer a disadvantage by participating in this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
Wang
Zhiyong Huang
About this study
Official title: Immunotherapy Using Precision T Cells Specific to Personalized Neo-antigen for the Treatment of Advanced Solid Tumor
The purpose of this study is to evaluate the safety, side effects and benefits of autologous tumor infiltrating lymphocytes (TIL) specific to personalized Neo-antigens in the treatment of patients with recurrent, metastatic and advanced solid tumors.
Read the detailed description
Adoptive cell transfer therapy that utilizes an autologous TIL manufacturing progress is originally developed by the NCI for the treatment of patients with recurrent, metastatic cervical cancer and liver cancer. TILs specific to personalized neo-antigens will be expended in vitro and given back to the patients through vein. A total of 20 patients will be enrolled in the single-arm, open label, interventional study.
- Conditions
- Recurrence Tumor, Metastatic Cancer, Solid Tumor
- Being tested
- TIL, Aldesleukin, Cyclophosphamide, Fludarabine
- Keywords
- TIL, neo-antigen, Cyclophosphamide, Fludarabine
- Medical subject headings
- Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TILBiological
On day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine)
AldesleukinDrug
Also called IL-2
IL-2 125,000 IU/kg/day IV (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks
CyclophosphamideDrug
Also called CTX
On day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
FludarabineDrug
Days -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days
| Study group | Role | What they receive |
|---|---|---|
| TIL,IL-2,Cyclophosphamide,Fludarabine | Experimental | Biological: TIL On day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Drug: Aldesleukin 125,000 IU/kg IV/day (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks) Drug: Cyclophosphamide On day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
Drug: Fludarabine Days -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days. Receives: Biological: TIL; Drug: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Responce Rate [Time Frame: 24 months after cell infusion]
The Objective Responce Rate of patients received immunotherapy are accesed by the Response Criteria in Solid Tumors (RECIST) v1.0.
Measured: 24 months after cell infusion
Secondary outcomes (5)
Adverse Event
Aggregate of all adverse events, as well as their frequency and severity are accessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.03).
Measured: up to 24 months
Disease Control Rate
Disease control rate (DCR) as measured by RECIST 1.1 criteria.
Measured: up to 24 months
Duration of Response
Duration of response (DOR) as measured by RECIST 1.1 criteria .
Measured: up to 24 months
Progression-Free Survival
PFS will be summarized using Kaplan-Meier estimates.
Measured: up to 24 months
Overall Survival
The overall survival of all patients entering the study will be monitored.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start28 Apr 2020
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
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 Recurrence TumorStudies of the same condition, open and under way.
- More trials run by Tongji HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Hui,MD, Tongji Hospital
- Investigators
- Hui Wang, MD, Study chair, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03658785
- Sponsor's protocol ID
- 2018TNB-V01
- Status last verified
- Aug 2024
- First submitted
- 3 Sep 2018
- Last updated
- 13 Aug 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Stevanovic S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015 May 10;33(14):1543-50. doi: 10.1200/JCO.2014.58.9093. Epub 2015 Mar 30.
PubMed 25823737Stevanovic S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA, Hinrichs CS. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017 Apr 14;356(6334):200-205. doi: 10.1126/science.aak9510.
PubMed 28408606Tran 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 24812403Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.
PubMed 29867227
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy Using Precision T Cells Specific to Personalized Neo-antigen for the Treatment of Advanced Solid Tumor
- ClinicalTrials.gov ID
- NCT03658785
- Acronym / sponsor ID
- 2018TNB-V01
- Conditions
- Recurrence Tumor, Metastatic Cancer, Solid Tumor
- Keywords
- TIL, neo-antigen, Cyclophosphamide, Fludarabine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 28 Apr 2020 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 5 Sep 2018 (actual)
- 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 purpose of this study is to evaluate the safety, side effects and benefits of autologous tumor infiltrating lymphocytes (TIL) specific to personalized Neo-antigens in the treatment of patients with recurrent, metastatic and advanced solid tumors.
Detailed description
Adoptive cell transfer therapy that utilizes an autologous TIL manufacturing progress is originally developed by the NCI for the treatment of patients with recurrent, metastatic cervical cancer and liver cancer. TILs specific to personalized neo-antigens will be expended in vitro and given back to the patients through vein. A total of 20 patients will be enrolled in the single-arm, open label, interventional study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TIL,IL-2,Cyclophosphamide,Fludarabine | Experimental | Biological: TIL, Drug: Aldesleukin, Drug: Cyclophosphamide, Drug: FludarabineBiological: TIL On day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine). Drug: Aldesleukin 125,000 IU/kg IV/day (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks) Drug: Cyclophosphamide On day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. Drug: Fludarabine Days -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- To be eligible for the study, patients must meet ALL of the following criteria prior to enrollment in the study:
- Must be ≥ 18 years of age at the time of consent.
- Must have recurrent, metastatic, or persistent carcinoma that is not amenable to curative treatment with surgery and/or radiation therapy and for which no other therapies are expected to have significant benefit, in the opinion of the Investigator.
- Must have at least 1 lesion that is resectable for TIL generation. The resected TIL generating lesion(s) should yield at least 1.5 cm in diameter post-resection of tumor tissue. Following resection for TIL generation, must have a remaining measurable target lesion as defined by RECIST v1.1.
- Patients must have progressive disease while receiving or after the completion of the most recent prior treatment.
Key exclusion criteria (12 listed)
- Patients who have received an organ allograft or prior cell transfer therapy.
- Patients who are on a systemic steroid therapy > 10 mg of prednisone daily or other steroid equivalent.
- Patients who currently have prior therapy-related toxicities greater than Grade 1 according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment/resection.
- Patients who have a contraindication to or history of hypersensitivity reaction to any component or excipients of the TIL therapy and the other study drugs.
- Patients with 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 |
|---|---|---|
| TILOn day 0, cells will be infused intravenously over 20 to 30 minutes (one to four days after the last dose of fludarabine) | Biological | TIL,IL-2,Cyclophosphamide,Fludarabine |
| AldesleukinAlso: IL-2IL-2 125,000 IU/kg/day IV (based on total body weight) beginning within 24 hours of cell infusion and continuing for up to 2 weeks | Drug | TIL,IL-2,Cyclophosphamide,Fludarabine |
| CyclophosphamideAlso: CTXOn day -7 and day -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. | Drug | TIL,IL-2,Cyclophosphamide,Fludarabine |
| FludarabineDays -5 to -1: Fludarabine 25 mg /m2/day IVPB daily over 30 minutes for 5 days | Drug | TIL,IL-2,Cyclophosphamide,Fludarabine |
Primary outcome
Objective Responce Rate [Time Frame: 24 months after cell infusion]
Time frame: 24 months after cell infusion
The Objective Responce Rate of patients received immunotherapy are accesed by the Response Criteria in Solid Tumors (RECIST) v1.0.
5 secondary outcomes
Adverse Event
Time frame: up to 24 months
Disease Control Rate
Time frame: up to 24 months
Duration of Response
Time frame: up to 24 months
Progression-Free Survival
Time frame: up to 24 months
Overall Survival
Time frame: up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Background: PubMed 25823737Stevanovic S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015 May 10;33(14):1543-50. doi: 10.1200/JCO.2014.58.9093. Epub 2015 Mar 30.
- Background: PubMed 28408606Stevanovic S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA, Hinrichs CS. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017 Apr 14;356(6334):200-205. doi: 10.1126/science.aak9510.
- Background: 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.
- Background: PubMed 29867227Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.
- Individual participant dataSharing planned: Undecided
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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.
Hui Wang, MD study chair
Tongji Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TIL, Aldesleukin and Cyclophosphamide in people with Recurrence Tumor and Metastatic Cancer, run by Tongji Hospital 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 14 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 13 Aug 2024. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hui Wang, MD (+8613995688388, huit71@sohu.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Responce Rate [Time Frame: 24 months after cell infusion] (time frame: 24 months after cell infusion). 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 NCT03658785, 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 13 Aug 2024.