Clinical trial NCT03634501: Clinical Study on Anti-tumor Effect Induced by Activated Primary Natural Killer（NK）Cells
Official title: Clinical Study on Anti-tumor Effect Induced by Activated Primary Natural Killer（NK）Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Breast Cancer
Colon Cancer
Pancreatic Cancer
Ovarian Cancer
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2018-08-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will analyze and evaluate the following items:

1. The safety of natural killer（NK） cells for treatment of subjects with solid tumors. Forty patients will be enrolled for each of the five cancers (in total 200 patients will be enrolled).
2. The effectiveness of natural killer（NK）cell therapy alone or with chemotherapy or targeted drugs.

Subjects from 18 to 75 years of age who are diagnosed with a solid tumor including pancreatic cancer, lung cancer, breast cancer, ovarian cancer and colon cancer, and for whom standard treatments are not effective, may be eligible for this study. Participants undergo the following procedures:

Peripheral blood will be collected from a vein of arm. Peripheral blood mononuclear cells（PBMC） will be isolated and purified for NK manufacturing. After 14\~21 days cultivation, activated NK will be harvested and formulated for clinical administration.

Subjects will receive NK cell treatment by intravenous infusion. The frequency is once every 3 or 4 weeks for the first 3 months. Participants who respond well after 3 months may be eligible to continue NK cell therapy; and those not may receive NK therapy combined with chemotherapy and/or targeted drugs, or chemotherapy/targeted drugs alone.

Evaluations during therapy including:

1. Clinical assessment, and history of medications;
2. Blood draws for routine and research tests, including but not limited to: lymphocyte population and circulating tumor cell analysis in peripheral blood;
3. CT scan, bone scan and positron emission tomography（PET ）scan, if indicated, for disease evaluation;
4. Pharmacokinetics study after NK infusion. For this test, the number of NK cells in the blood is measured over time at indicated time-points.


Eligibility criteria: Inclusion Criteria:

1. Age from 18 to 75 years (including boundary values);
2. Diagnosed with histologically and cellularly confirmed cancer of lung, breast, pancreas, ovary, or colon;
3. At least 8 weeks since any prior systemic therapy to treat the underlying malignancy (standard or investigational);
4. Life expectancy \> 6 months, and performance status（KPS）\> 60 points;
5. Organ functions meet the following criteria:

   1. Blood bilirubin \< 2mg/dL,
   2. Aspartate transaminase（AST）\<100 IU/L,
   3. Alanine transaminase（ALT） \<100 IU/L,
   4. Creatinine \<1.5 mg/dL,
   5. Urea nitrogen ≤ 25 mg/dL,
   6. Hemoglobin ≥ 9.0 g/dL,
   7. White blood cell count\>3.5×109/L,
   8. Neutrophil count \>1.5x109/L,
   9. Platelet count \> 80 × 109 /L,
   10. Hematocrit \>0.20,
6. No severe infections.

Exclusion Criteria:

1. Subjects who take combined systemic steroids within 2 weeks prior to treatment (except inhaled steroids);
2. Patients who take chemotherapy within 1 month prior to treatment;
3. Subjects receiving drugs that stimulate the production of bone marrow hematopoietic cells within two weeks prior to treatment;
4. Patients with T lymphoma and NK cell lymphoma;
5. Patients with autoimmune diseases, including but not limited to lupus erythematosus, rheumatoid arthritis, etc.;
6. Seriously uncontrollable infected patients;
7. Patients who are allergic to the biological agents in this treatment;
8. Patients with organ transplantation or organ failure;
9. Subjects with severe cardiovascular disease and severe renal failure;
10. Patients who are undergoing treatment of immunosuppressive drugs or long-term administration of immunosuppressive drugs after organ transplantation;
11. Patients with active infection or fever;
12. Subjects with severe cardiovascular and cerebrovascular diseases, diabetes and renal dysfunction;
13. Subjects with pregnancy or during the lactating period.

Primary outcomes:
measure: Incidence of toxicity induced by NK infusion
timeFrame: 6 months
Secondary outcomes:
measure: Objective-response rate (ORR)
timeFrame: 6 months after 6 infusions of NK administration
measure: Persistence of NK
timeFrame: Day 0, Day 7, Day30, Day 60, Day 90, Day 180
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Zhiguo Chen, PhD
role: STUDY_DIRECTOR
References: