Clinical Study of Granulocyte Infusion for Advanced Cancer

NCT04124666 | Unknown Phase 1 DMC

• 1 other identifier: KY2019-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The trial will observe the subject's progression free survival for 3 months after the granulocyte infusions are completed.

  90 days post treatment

Secondary Outcomes (5)

• median Overall Survival (mOS)

  180 days post treatment

• Objective Response Rate (ORR )

  180 days post treatment

• Disease Control Rate (DCR)

  180 days post treatment

• Quality of life measured in ECOG

  180 days post treatment

• Treatment-related adverse events

  5 weeks of treatment and 1 month post treatment

Study Arms (1)

Granulocytes infusion only

EXPERIMENTAL

Fresh, non-irradiated granulocytes from ABO, Rh, CMV compatible, unrelated donors; bioactivity of anti-cancer ability meets the criteria.

Biological: Granulocytes

Interventions

Granulocytes BIOLOGICAL

Granulocytes cross-matched for ABO-Rh and CMV; bioactivity of anti-cancer ability meets the criteria.

Granulocytes infusion only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ≥ 4 weeks since prior medical therapy, radiation therapy, and surgery
• Laboratory tests meet the following criteria:
• A. Bone marrow function: Absolute blood neutrophil (ANC) count ≥1\*10\^9 /L, blood small (PLT) ≥75\*10\^9 /L.
• B. 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);
• C. 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.

You may not qualify if:

• 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;
• 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.
• 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;

Sponsors & Collaborators

• Shanghai East Hospital: lead

Study Sites (1)

Department of Oncology, Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

RECRUITING

Study Officials

• Zhongming Liu, MD/Ph.D

  Shanghai East Hospital, Shanghai Tongji University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenjun Le, Ph.D

CONTACT

(+86)-21-38804518; wenjunle@tongji.edu.cn

Zhongming Liu, MD/Ph.D

CONTACT

(+86)-21-38804518; liu.zhongmin@tongji.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: October 11, 2019
• Study Start: December 1, 2019
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: December 19, 2019

Record last verified: 2019-12

Locations

CN (1)