Advanced CancerPhase 1/2NCT04124666
Clinical Study of Granulocyte Infusion for Advanced Cancer
A Phase 1/2 study testing Granulocytes in people with Advanced Cancer, run by Shanghai East Hospital at 1 site in China.
Trial summary
Background \& Rationale: For years, most tumor immunotherapy researches have focused on T cell and natural killer (NK) cell therapies, most of which involve amplification and modification of the patient's immune cells for reinfusion therapy. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- Granulocytes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2019to 30 Sep 2022
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Malignant tumor confirmed by puncture pathology/postoperative pathology;
- Clinical stage IV;
- Performance status of ≤2 on the ECOG scale
- Life expectancy of at least 3 months
- All patients was diagnosed metastatic tumor by histology and cytology. Cytoreductive surgery can be performed if the patient can endure surgery.
- Measurable Disease: Lesions that can be accurately measured in at least one dimension (longest diameter recorded) as 20 mm with conventional technique or as 10 mm with spiral CT scan.If the lesion is between 15mm and 20mm, the thickness of the CT layer should be no more than 0.5mm. For multiple lesions, select a representative 10 lesions (maximum 5 in the same organ) and calculate the sum of the longest diameters of all target lesions as the baseline sum diameter.
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- ≥ 4 weeks since prior medical therapy, radiation therapy, and surgery
- Laboratory tests meet the following criteria:
- Bone marrow function: Absolute blood neutrophil (ANC) count ≥1*10^9 /L, blood small (PLT) ≥75*10^9 /L.
- Liver function: serum total bilirubin (STB), combined bilirubin (CB) ≤ upper limit of normal (ULN) * 1.5, alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ULN*2.5 (in the absence of liver metastases), or ≤ULN*5 (with liver metastases);
- Renal function: serum creatinine (Cr) ≤ ULN * 1.5, endogenous creatinine clearance (Ccr) ≥ 50 mL / min (calculated using the Cockcroft-Gault formula, see Appendix 2);
- The anti-neutrophil antibody test result was negative.
- The patient volunteered and signed an informed consent form.
- Must have signed Donor-participant Informed Consent Form
- Must be able to provide granulocytes in local blood donation center, and transport collected granulocytes to the hospital blood bank or clinical application within 24 hours;
- Must score >80% in Cancer Killing Assay (CKA), a score of 60-80% would be considered when there are insufficient donors;
- Must have CMV negative or positive sero-testing completed; only seronegative donors are accepted for a seronegative recipient;
- Must have compatible ABO and RH typing with the recipient;
- Must be qualified for blood donation: aged 18-35, male >50kg or female >45kg, normal cardiopulmonary function, specific gravity of blood male≥1.052 or female≥1.051, HbsAg, anti-HCV, anti-HIV, or syphilis tests.
Who cannot join
- Arrhythmia, congestive heart failure, or severe coronary artery disease;
- Pregnant or nursing women;
- Patients with severe autoimmune diseases;
- Patients who have been using or are using immunosuppressive agents for a long time;
- Those with coagulopathy;
- Cases that the investigator considered inappropriate for inclusion.
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- Dental or other minor surgery within preceding 15 days;
- Arrhythmia, congestive heart failure, or severe coronary artery disease;
- Major surgery within preceding 6 months;
- Appendectomy, hernia repair, or tonsillectomy within preceding 3 months;
- Females 3 days before or after menstruation, ≤6 months since prior pregnancy or abortion, ≤ 1 year since delivery/breastfeeding;
- Recovery from flu or acute gastroenteritis within preceding week, acute renal infection within preceding month, pneumonia within preceding 3 months;
- Recovery from infectious diseases such as dysentery within preceding 6 months, typhoid fever within preceding year, brucellosis within preceding 2 years, or malaria within preceding 3 years;
- Recovery from localized dermatitis within preceding week, extensive inflammation within preceding 2 weeks;
- Receiving whole blood or blood components within preceding 5 years;
- Allergic to G-CSF mobilizer.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Oncology, Shanghai East Hospital
Shanghai, Shanghai Municipality, 200123
Yifan Zhang, +86-021-38804518-22203
About this study
Official title: Clinical Study of Allogeneic Granulocyte Infusion in the Treatment of Patients With Advanced Cancer
Background \& Rationale:
For years, most tumor immunotherapy researches have focused on T cell and natural killer (NK) cell therapies, most of which involve amplification and modification of the patient's immune cells for reinfusion therapy. However, for the treatment of solid tumors, there is currently little breakthrough. Recently, researchers have reported a colony of cancer-resistant mice developed from a single mouse that was immune to multiple lethal cancer cell injections. Further research revealed that such anti-cancer immunity can cause rapid shrinkage or disappearance of the tumors in other cancer-bearing mice. Interestingly, this therapeutic effect is due to the donor granulocytes, instead of T cells or NK cells. Infusion of granulocytes is a classic therapy in treating infection associated with granulocytopenia. Currently, clinical collection of blood components, including isolation of granulocytes, is a mature technique. The infusion of granulocytes is a viable anticancer therapy combining the classic technique and novel anticancer approach. This proposed trial will test whether granulocyte infusions from healthy unrelated donors can be used to treat advanced cancer. In the proposed trial, up to 100 Subjects with advanced cancer can be entered. Each patient will be given a dose of (2.0-5.0)x10^10 granulocytes from a different healthy donor every week over a course of 5 doses. The trial will evaluate the subject's cancer 7, 30, 90 and 180 days after the last infusion.
Read the detailed description
Granulocyte anti-cancer therapy refers to a method in which healthy donor granulocytes with high cancer-killing activity are collected and infused into a specific cancer patient by matching, to achieve the therapeutic anticancer effect. In this proposed trial, up to 100 Subjects with advanced cancer can be entered. Potentially hundreds of healthy Donor-participants will be recruited. First, granulocyte donors will be identified via in-vitro assay of Cancer Killing Activity (CKA), which screens healthy Donor-participants for those with anticancer activity of more than 80%. Secondly, after donor-recipient blood matching, (2.0-5.0)x10^10 granulocytes will be collected from each donor, accounting for about 1/10 of the human body. Each patient will be given a dose of (2.0-5.0)x10^10 granulocytes from a different donor per week over a course of 5 doses (with an ideal total infusion of 2X10^11 granulocytes). After each infusion, the patients will be monitored carefully for possible adverse events. If adverse events occur, the infusion can be slowed down or stopped until the adverse events can be managed. The trial will observe the subject's cancer 7, 30, 90 and 180 days after the last infusion. Target lesions, non-target lesions, and new lesions will be evaluated via medical imaging and tumor markers. The responses will be compared against the measurements at baseline.
- Conditions
- Advanced Cancer
- Being tested
- Granulocytes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GranulocytesBiological
Granulocytes cross-matched for ABO-Rh and CMV; bioactivity of anti-cancer ability meets the criteria.
| Study group | Role | What they receive |
|---|---|---|
| Granulocytes infusion only | Experimental | Fresh, non-irradiated granulocytes from ABO, Rh, CMV compatible, unrelated donors; bioactivity of anti-cancer ability meets the criteria. Receives: Biological: Granulocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
The trial will observe the subject's progression free survival for 3 months after the granulocyte infusions are completed.
Measured: 90 days post treatment
Secondary outcomes (5)
median Overall Survival (mOS)
The patients will be followed 1 week, 1 month, 3 months and 6 months after the last treatment. Median Overall Survival will be measured as the length of time from the date of inclusion that half of the patients are still alive.
Measured: 180 days post treatment
Objective Response Rate (ORR )
Objective Response Rate will be evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. If a response is achieved in a patient, the evaluation will be repeated 4-6 weeks after the first evaluation to confirm the response.
Measured: 180 days post treatment
Disease Control Rate (DCR)
Disease Control Rate will be measured as the percentage of patients achieved complete response (CR), partial response (PR) and stable disease (SD) to the treatment (evaluated based on RECIST 1.1).
Measured: 180 days post treatment
Quality of life measured in ECOG
ECOG Scale of Performance Status will be evaluated for patients after treatment to reflect impact on quality of life.
Measured: 180 days post treatment
Treatment-related adverse events
Incidence of treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: 5 weeks of treatment and 1 month post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2019
- Study start1 Dec 2019
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai East Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhongming Liu, MD/Ph.D, Principal investigator, Shanghai East Hospital, Shanghai Tongji University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04124666
- Sponsor's protocol ID
- KY2019-01
- Status last verified
- Dec 2019
- First submitted
- 10 Sep 2019
- Last updated
- 19 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Allogeneic Granulocyte Infusion in the Treatment of Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT04124666
- Acronym / sponsor ID
- KY2019-01
- Conditions
- Advanced Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shanghai East HospitalUniversity, hospital or other
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 11 Oct 2019 (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.
Background \& Rationale:
For years, most tumor immunotherapy researches have focused on T cell and natural killer (NK) cell therapies, most of which involve amplification and modification of the patient's immune cells for reinfusion therapy. However, for the treatment of solid tumors, there is currently little breakthrough. Recently, researchers have reported a colony of cancer-resistant mice developed from a single mouse that was immune to multiple lethal cancer cell injections. Further research revealed that such anti-cancer immunity can cause rapid shrinkage or disappearance of the tumors in other cancer-bearing mice. Interestingly, this therapeutic effect is due to the donor granulocytes, instead of T cells or NK cells. Infusion of granulocytes is a classic therapy in treating infection associated with granulocytopenia. Currently, clinical collection of blood components, including isolation of granulocytes, is a mature technique. The infusion of granulocytes is a viable anticancer therapy combining the classic technique and novel anticancer approach. This proposed trial will test whether granulocyte infusions from healthy unrelated donors can be used to treat advanced cancer. In the proposed trial, up to 100 Subjects with advanced cancer can be entered. Each patient will be given a dose of (2.0-5.0)x10^10 granulocytes from a different healthy donor every week over a course of 5 doses. The trial will evaluate the subject's cancer 7, 30, 90 and 180 days after the last infusion.
Detailed description
Granulocyte anti-cancer therapy refers to a method in which healthy donor granulocytes with high cancer-killing activity are collected and infused into a specific cancer patient by matching, to achieve the therapeutic anticancer effect. In this proposed trial, up to 100 Subjects with advanced cancer can be entered. Potentially hundreds of healthy Donor-participants will be recruited. First, granulocyte donors will be identified via in-vitro assay of Cancer Killing Activity (CKA), which screens healthy Donor-participants for those with anticancer activity of more than 80%. Secondly, after donor-recipient blood matching, (2.0-5.0)x10^10 granulocytes will be collected from each donor, accounting for about 1/10 of the human body. Each patient will be given a dose of (2.0-5.0)x10^10 granulocytes from a different donor per week over a course of 5 doses (with an ideal total infusion of 2X10^11 granulocytes). After each infusion, the patients will be monitored carefully for possible adverse events. If adverse events occur, the infusion can be slowed down or stopped until the adverse events can be managed. The trial will observe the subject's cancer 7, 30, 90 and 180 days after the last infusion. Target lesions, non-target lesions, and new lesions will be evaluated via medical imaging and tumor markers. The responses will be compared against the measurements at baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Granulocytes infusion only | Experimental | Biological: GranulocytesFresh, non-irradiated granulocytes from ABO, Rh, CMV compatible, unrelated donors; bioactivity of anti-cancer ability meets the criteria. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Malignant tumor confirmed by puncture pathology/postoperative pathology;
- Clinical stage IV;
- Performance status of ≤2 on the ECOG scale
- Life expectancy of at least 3 months
- All patients was diagnosed metastatic tumor by histology and cytology. Cytoreductive surgery can be performed if the patient can endure surgery.
Key exclusion criteria (16 listed)
- Arrhythmia, congestive heart failure, or severe coronary artery disease;
- Pregnant or nursing women;
- Patients with severe autoimmune diseases;
- Patients who have been using or are using immunosuppressive agents for a long time;
- Those with coagulopathy;
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 |
|---|---|---|
| GranulocytesGranulocytes cross-matched for ABO-Rh and CMV; bioactivity of anti-cancer ability meets the criteria. | Biological | Granulocytes infusion only |
Primary outcome
Progression free survival (PFS)
Time frame: 90 days post treatment
The trial will observe the subject's progression free survival for 3 months after the granulocyte infusions are completed.
5 secondary outcomes
median Overall Survival (mOS)
Time frame: 180 days post treatment
Objective Response Rate (ORR )
Time frame: 180 days post treatment
Disease Control Rate (DCR)
Time frame: 180 days post treatment
Quality of life measured in ECOG
Time frame: 180 days post treatment
Treatment-related adverse events
Time frame: 5 weeks of treatment and 1 month post treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
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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.
Zhongming Liu, MD/Ph.D principal investigator
Shanghai East Hospital, Shanghai Tongji University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Granulocytes in people with Advanced Cancer, run by Shanghai East 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 19 inclusion and 16 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 19 Dec 2019. 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 Wenjun Le, Ph.D ((+86)-21-38804518, wenjunle@tongji.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: 90 days post 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 19 Dec 2019.