Malignant Pleural EffusionEarly Phase 1NCT05565014
Safety and Efficacy Study of Virus Activated Killer Immune Cells (VAK) for Malignant Pleural and Peritoneal Effusion
A Early Phase 1 study testing Virus Activated Killer immune Cells and Saline in people with Malignant Pleural Effusion and Malignant Peritoneal Effusion, run by Sheng Hu at 1 site in China.
Trial summary
Theory of VAK： 1. Immune cells (T cells for example) of cancer subjects may be domesticated by the tumor microenvironment, and have low efficacy to kill cancer cells. They could be restimulated by virus antigen, and play a powerful tumor killing role while intrapleural to subjects. 2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Effusion, Malignant Peritoneal Effusion
- What is being tested?
- Virus Activated Killer immune Cells and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 24 Jul 2020to 30 Jun 2024
- Phase
- Early 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing to sign informed consent;
- Pathological confirmed advanced malignant tumor with malignant pleural or peritoneal effusion;
- Vital signs stable, Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
- Age ≥ 18 years old, gender unlimited;
- Expected survival period more than 3 months;
- Subjects agree to take effective contraceptive measures at the time of enrollment and within 4 months after enrollment. The pregnancy test of female patients must be negative;
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- Sufficient bone marrow, liver and kidney functions. Laboratory tests within 7 days before the first drug use meet the following requirements:
- Coagulation function: APTT ≤ 1.5 × ULN, while INR or PT ≤ 1.5 × ULN (not receiving anticoagulant therapy); ② Blood routine examination: Hgb ≥ 80g / L, WBC > 3 × 10^9/L、NEU≥1.0 × 10^9/L、PLT≥80 × 10^9/L;
- Liver function: total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); AST and alt ≤ 2.5 times ULN (if abnormal liver function is mainly caused by tumor infiltration, it can be ≤ 5 times ULN; alkaline phosphatase ≤ 2.5 times ULN; ④ Renal function: bun and Cr ≤ 1.5 times ULN, creatinine clearance ≥ 40ml / min (calculated by Cockcroft Gault formula).
Who cannot join
- Subjects requiring emergency treatment due to intestinal obstruction or vascular compression;
- Subjects with active hemolytic anemia;
- Subjects with active central nervous system metastases were excluded, except those with brain metastases or asymptomatic cancer cells found in cerebrospinal fluid;
- Pregnant or lactating female;
- Systemic active infection, serious coagulation disorder or serious heart, respiratory and immune system diseases;
- Congenital or acquired immune function defects (such as HIV infection), hepatitis B infection (HBV-DNA ≥ 10 ^ 4 / ml), hepatitis C infection (HCV antibody and HCV RNA positive);
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- Subjects who had serious infection within 4 weeks before the first medication were excluded, including but not limited to infectious complications, bacteremia and severe pneumonia requiring hospitalization;
- Subjects with active autoimmune diseases or a history of autoimmune diseases that may recur, but the following are not excluded:
- Type 1 diabetes
- Hypothyroidism (if controlled by hormone replacement therapy only)
- Controlled celiac disease ④ Skin diseases without systemic treatment (such as vitiligo, psoriasis, alopecia) ⑤ Any other disease that does not recur without external triggers.
- Those who had severe hypersensitivity to the drugs used in this protocol in the past;
- Subjects who are ready for or have previously received tissue / organ transplantation;
- Subjects with large pericardial effusion were excluded;
- Exclude those who have suffered from other malignant tumors within 2 years, except for cervical carcinoma in situ, low-risk gastrointestinal stromal tumor, skin basal cell carcinoma, skin squamous cell carcinoma, thyroid papillary carcinoma and breast ductal carcinoma in situ that have been effectively removed;
- Exclude subjects who have been vaccinated or will be vaccinated with live vaccine within 4 weeks before the first administration;
- Other circumstances that the investigator considers inappropriate for clinical trials.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Sheng Hu, MD, 15377602179, ehusmn@163.com
Shuang Dong, UK, 15802766720, dongshuang_2008@163.com
About this study
Official title: An Open Label, Randomized Controlled Clinical Study on the Safety and Efficacy of Virus Activated Killer Immune Cells (VAK) in the Treatment of Malignant Pleural and Peritoneal Effusion
Theory of VAK：
- Immune cells (T cells for example) of cancer subjects may be domesticated by the tumor microenvironment, and have low efficacy to kill cancer cells. They could be restimulated by virus antigen, and play a powerful tumor killing role while intrapleural to subjects.
- Releasing of tumor-associated antigen could induce specific anti-tumor immune response.
Preparation of VAK：
- Separate the immune cells and tumor cells from Malignant Pleural and Peritoneal Effusion.
- Incubate the immune cells with inactivated viruses and tumor cells.
- Wash to remove impurities.
- Intrapleural the immune cells to patients
Read the detailed description
There are a large number of immune cells in immune tolerance state in the tumor microenvironment. The theoretical basis of this clinical study is to use ultraviolet inactivated oncolytic herpes simplex virus type 2 (UV-oHSV2) to activate PBMC or immune cells in immune tolerance state in malignant pleural and peritoneal fluid in vitro, and to transfusion the activated immune cells back to the patient's peripheral blood or pleural and peritoneal fluid to kill tumor cells in malignant pleural and peritoneal fluid to further control the volume of malignant pleural and peritoneal fluid.
Our study indicated that UV-oHSV2 potently activated human peripheral blood mononuclear cells leading to increased antitumor activity in vitro and in vivo. We also found that UV-oHSV2 could induce NK cells (isolated from healthy donors' PBMC or patient pleural effusion) proliferation, secretion of IFN-γ. We further found that UV-oHSV2 could enhance NK cells (isolated from healthy PBMC or patient pleural effusion) antitumor ability in vitro and in vivo.
Based on the above research, we carried out an open, single center, prospective clinical trial to evaluate the safety and effectiveness of VAK cells in the treatment of malignant pleural and peritoneal effusions.
The detailed protocol as follow:
Isolation of lymphocytes from the patient's pleural effusions or ascites:
- Add pleural fluid into a 50ml centrifuge tube, centrifuge at 400g, and discard the supernatant.
- Resuspend the precipitate with 40ml of normal saline and pass through 70 μ M U.M and then rinse the cell filter once with 5ml physiological saline.
- Discard the cell filter, and centrifuge the filtered cell suspension in the centrifuge tube at 400g for 5min. After centrifugation, discard the supernatant and resuspend the cell pellet with 5ml of normal saline.
- Mix Ficoll upside down before use, take a new 15ml centrifuge tube and add 5ml Ficoll (suck with syringe).
- Gently add 5-6ml cell suspension onto Ficoll layer.
- Centrifuge 400g, 30-40min, 18 ℃ - 20 ℃, the centrifuge needs to be slowly raised and lowered, and the sudden stop braking setting should be closed.
- Take the middle white membrane layer (lymphocytes) into a new centrifuge tube.
- Add 3 times the volume of normal saline to the absorbed lymphocytes, resuspend the cells, centrifuge 400-500g, 10-15min, 18 ℃ - 20 ℃.
- Repeat washing once, and the final precipitate is resuspended with 5ml serum-free medium (RPMI1640).
- Take 20 μ L of cell suspension in EP tube, add equal volume of trypan blue staining solution, gently blow and count with cell counter.
- In the process of planting the isolated immune cells, the cell culture density was controlled within the range of 106, and 10% autologous plasma was added.
- Take 4ml of cell suspension for separate culture, and add the corresponding amount of inactivated virus to the remaining cell suspension with the infection number MOI = 1. The calculation formula is as follows: volume of uv-oh2 added = (1 × Number of cells added per well plate or bottle / oh2 virus titer)
- After the immune cells are planted, they are placed in a 5% CO2 incubator for 36h-48h.
After cell culture, 30-50ML of prepared lymphocytes (qualified by PCR sterility test and endotoxin test) were infused into the chest and abdominal cavity of the patient.
- Being tested
- Virus Activated Killer immune Cells, Saline
- Medical subject headings
- Pleural Effusion, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Virus Activated Killer immune CellsDrug
Also called VAK
The VAK made from Pleural Effusion should be given to treat Malignant Pleural Effusion.The VAK made from Peritoneal Effusion should be given to treat Malignant Peritoneal Effusion.
SalineDrug
The use of saline was the same as VAK group.
| Study group | Role | What they receive |
|---|---|---|
| Virus Activated Killer immune Cells（VAK） | Experimental | The VAK should be given once a week, three times a circle. The VAK could given 1 or 2 circle for each subject. The dosage of Pleural Effusion（more than 10^5/kg cells in 30-50mL solvent） differs from Peritoneal Effusion（more than 10^4/kg cells in 30-50mL solvent） Receives: Drug: Virus Activated Killer immune Cells |
| saline | Placebo comparator | 50ml of saline was injected once a week,three times a circle.The saline could given 1 or 2 circle for each subject. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of AEs and SAEs
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: 28 days after the last treatment.
Secondary outcomes (3)
ORR of Malignant Pleural and Peritoneal Effusion by WHO 1997
The volume of pleural and peritoneal effusion was measured by volume software of spiral CT machine to determine the change of pleural and peritoneal effusion volume before and after treatment. ORR=PR+CR.
Measured: 28 days after the last treatment.
Progression Free Survival
Progression free survival from day 1 of treatment until death or progression.
Measured: up to 1 year.
Overall Survival
Overall survival from day 1 of treatment until death.
Measured: up to 2 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start24 Jul 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural EffusionStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheng Hu
- Sponsor type
- University, hospital or other
- Collaborators
- Binhui Biopharmaceutical Co., Ltd.
- Responsible party
- Sponsor-investigator, Sheng Hu, Hubei Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05565014
- Sponsor's protocol ID
- HBCHC03
- Status last verified
- Sep 2022
- First submitted
- 29 Sep 2022
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomized Controlled Clinical Study on the Safety and Efficacy of Virus Activated Killer Immune Cells (VAK) in the Treatment of Malignant Pleural and Peritoneal Effusion
- ClinicalTrials.gov ID
- NCT05565014
- Acronym / sponsor ID
- HBCHC03
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Sheng HuUniversity, hospital or other
- Collaborators
- Binhui Biopharmaceutical Co., Ltd.
- Study start
- 24 Jul 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 4 Oct 2022 (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.
Theory of VAK：
- Immune cells (T cells for example) of cancer subjects may be domesticated by the tumor microenvironment, and have low efficacy to kill cancer cells. They could be restimulated by virus antigen, and play a powerful tumor killing role while intrapleural to subjects.
- Releasing of tumor-associated antigen could induce specific anti-tumor immune response.
Preparation of VAK：
- Separate the immune cells and tumor cells from Malignant Pleural and Peritoneal Effusion.
- Incubate the immune cells with inactivated viruses and tumor cells.
- Wash to remove impurities.
- Intrapleural the immune cells to patients
Detailed description
There are a large number of immune cells in immune tolerance state in the tumor microenvironment. The theoretical basis of this clinical study is to use ultraviolet inactivated oncolytic herpes simplex virus type 2 (UV-oHSV2) to activate PBMC or immune cells in immune tolerance state in malignant pleural and peritoneal fluid in vitro, and to transfusion the activated immune cells back to the patient's peripheral blood or pleural and peritoneal fluid to kill tumor cells in malignant pleural and peritoneal fluid to further control the volume of malignant pleural and peritoneal fluid.
Our study indicated that UV-oHSV2 potently activated human peripheral blood mononuclear cells leading to increased antitumor activity in vitro and in vivo. We also found that UV-oHSV2 could induce NK cells (isolated from healthy donors' PBMC or patient pleural effusion) proliferation, secretion of IFN-γ. We further found that UV-oHSV2 could enhance NK cells (isolated from healthy PBMC or patient pleural effusion) antitumor ability in vitro and in vivo.
Based on the above research, we carried out an open, single center, prospective clinical trial to evaluate the safety and effectiveness of VAK cells in the treatment of malignant pleural and peritoneal effusions.
The detailed protocol as follow:
Isolation of lymphocytes from the patient's pleural effusions or ascites:
- Add pleural fluid into a 50ml centrifuge tube, centrifuge at 400g, and discard the supernatant.
- Resuspend the precipitate with 40ml of normal saline and pass through 70 μ M U.M and then rinse the cell filter once with 5ml physiological saline.
- Discard the cell filter, and centrifuge the filtered cell suspension in the centrifuge tube at 400g for 5min. After centrifugation, discard the supernatant and resuspend the cell pellet with 5ml of normal saline.
- Mix Ficoll upside down before use, take a new 15ml centrifuge tube and add 5ml Ficoll (suck with syringe).
- Gently add 5-6ml cell suspension onto Ficoll layer.
- Centrifuge 400g, 30-40min, 18 ℃ - 20 ℃, the centrifuge needs to be slowly raised and lowered, and the sudden stop braking setting should be closed.
- Take the middle white membrane layer (lymphocytes) into a new centrifuge tube.
- Add 3 times the volume of normal saline to the absorbed lymphocytes, resuspend the cells, centrifuge 400-500g, 10-15min, 18 ℃ - 20 ℃.
- Repeat washing once, and the final precipitate is resuspended with 5ml serum-free medium (RPMI1640).
- Take 20 μ L of cell suspension in EP tube, add equal volume of trypan blue staining solution, gently blow and count with cell counter.
- In the process of planting the isolated immune cells, the cell culture density was controlled within the range of 106, and 10% autologous plasma was added.
- Take 4ml of cell suspension for separate culture, and add the corresponding amount of inactivated virus to the remaining cell suspension with the infection number MOI = 1. The calculation formula is as follows: volume of uv-oh2 added = (1 × Number of cells added per well plate or bottle / oh2 virus titer)
- After the immune cells are planted, they are placed in a 5% CO2 incubator for 36h-48h.
After cell culture, 30-50ML of prepared lymphocytes (qualified by PCR sterility test and endotoxin test) were infused into the chest and abdominal cavity of the patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Virus Activated Killer immune Cells（VAK） | Experimental | Drug: Virus Activated Killer immune CellsThe VAK should be given once a week, three times a circle. The VAK could given 1 or 2 circle for each subject. The dosage of Pleural Effusion（more than 10^5/kg cells in 30-50mL solvent） differs from Peritoneal Effusion（more than 10^4/kg cells in 30-50mL solvent） |
| saline | Placebo comparator | Drug: Saline50ml of saline was injected once a week,three times a circle.The saline could given 1 or 2 circle for each subject. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Willing to sign informed consent;
- Pathological confirmed advanced malignant tumor with malignant pleural or peritoneal effusion;
- Vital signs stable, Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
- Age ≥ 18 years old, gender unlimited;
- Expected survival period more than 3 months;
Key exclusion criteria (17 listed)
- Subjects requiring emergency treatment due to intestinal obstruction or vascular compression;
- Subjects with active hemolytic anemia;
- Subjects with active central nervous system metastases were excluded, except those with brain metastases or asymptomatic cancer cells found in cerebrospinal fluid;
- Pregnant or lactating female;
- Systemic active infection, serious coagulation disorder or serious heart, respiratory and immune system diseases;
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 |
|---|---|---|
| Virus Activated Killer immune CellsAlso: VAKThe VAK made from Pleural Effusion should be given to treat Malignant Pleural Effusion.The VAK made from Peritoneal Effusion should be given to treat Malignant Peritoneal Effusion. | Drug | Virus Activated Killer immune Cells（VAK） |
| SalineThe use of saline was the same as VAK group. | Drug | saline |
Primary outcome
Incidence of AEs and SAEs
Time frame: 28 days after the last treatment.
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
3 secondary outcomes
ORR of Malignant Pleural and Peritoneal Effusion by WHO 1997
Time frame: 28 days after the last treatment.
Progression Free Survival
Time frame: up to 1 year.
Overall Survival
Time frame: up to 2 year.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Virus Activated Killer immune Cells and Saline in people with Malignant Pleural Effusion and Malignant Peritoneal Effusion, run by Sheng Hu 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 9 inclusion and 17 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 4 Oct 2022. 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. Some participants in this study may receive a placebo. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Sheng Hu, MD (15377602179, ehusmn@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of AEs and SAEs (time frame: 28 days after the last treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Oct 2022.