Study on the Safety and Effectiveness of UCB-NK Cell Infusion in the Treatment of Advanced Gastric Cancer and Gastroesophageal Cancer

NCT04385641 | Unknown

• 1 other identifier: IH-UCB-NK-422
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open, single infusion, cell infusion dose /method exploration study. In patients with gastric cancer and gastroesophageal cancer without effective treatment, the safety of UCB-NK cell immunotherapy was evaluated and the preliminary curative effect results were obtained.

Conditions

Advanced Gastric Cancer; Gastroesophageal Cancer

Keywords

UCB-NK cell infusion; safety; effectiveness

Outcome Measures

Primary Outcomes (3)

• Safety assessment

  Evaluation of adverse events and severity according to CTCAE v5.0

  4 weeks

• Hematology toxicity

  After 7 days of treatment, the ≥ 4 degree hematotoxicity (excluding lymphocyte reduction) related to UCB-NK treatment could not recover to ≤ 3 degree

  7 days

• Non hematologic toxicity

  Any non hematologic toxic reaction≥4 degree related to UCB-NK treatment cannot be reduced to≤3 degree within 3 days and no further improvement is found; Gastric mucosal injury including gastric hemorrhage≥3 degree related to UCB-NK treatment; Other non hematologic toxicity≥3 degree related to UCB-NK treatment lasted for more than 7 days.

  7 days

Secondary Outcomes (1)

• Tumor assessment

  4 years

Study Arms (2)

Dose-finding (Group A)

EXPERIMENTAL

In this study, the dose was explored according to the "3+3" mode, in which group A was divided into three dose groups: 1.5\*10＾9 group, 2\*10＾9 group and 3\*10＾9 group. If DLT occurs in one of the first three subjects in each dose group within four weeks after cell infusion, three subjects will continue to be included. If more than 1/6 cases of DLT appear in 6 subjects with 1.5\*10＾9 dose, the dose level and/or cell infusion frequency and method will be reduced after discussion between the investigator, the collaborator and DMC. If DLT did not occur in the first 3 subjects within 4 weeks after receiving 1.5\*10＾9 cell infusion，another three subjects were enrolled into the group received 2\*10＾9 cell infusion. DLT did not occur within 4 weeks after cell infusion, it will increase to 3\*10＾9 dose group. That is to say, the first three subjects were included for observation for 4 weeks in the 3\*10＾9 dose group, if DLT did not occur, there will be another 3 cases, reaching to 6 subjects.

Other: Cell infusion for Dose-finding (Group A)

Extended research (Group B)

EXPERIMENTAL

If DLT≤1/6, the dose will not be increased. This dose will also be used as the treatment dose of group B. If DLT is more than 1/6 in the 3\*10＾9 dose group, three subjects will be added in 2\*10＾9 dose group. If DLT ≤1/6 in 4-week observation, the 2\*10＾9 will be the maximum tolerable dose, and will be used as the treatment dose of group B. The subjects in group A were enrolled first, after at least 4 weeks of observation for all subjects, six subjects will be included in group B.

Other: Cell infusion for Extended research (Group B)

Interventions

Cell infusion for Dose-finding (Group A) OTHER

Group A：HLA-I and HLA-II molecular typing were performed at the serological and molecular levels, and the HLA-I and HLA-II molecular antigens of donor and subjects match on 3, 4, 5 or 6 / 6. After the successful matching, the non myeloablative immunosuppressive pretreatment with cyclophosphamide (900 mg / m＾2 / day) and fludarabine (30 mg / m＾2 / day) will be performed 6, 5, 4 and 3 days before the infusion of UCB-NK cells. After the pretreatment, the cell infusion was started on day 0, and the cell infusion could be divided into 50% and 50% for two consecutive days or every other day. To ensure clinical safety, if treatment-related adverse events reach DLT after the first infusion, the cell infusion will stop.

Dose-finding (Group A)

Cell infusion for Extended research (Group B) OTHER

Group B：Non myeloablative immunosuppressive pretreatment and cell transfusion were the same as group A.

Extended research (Group B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• )Patients with advanced gastric cancer or gastroesophageal cancer confirmed by pathology and failed in standard treatment; 2)ECOG scores≤1； 3)Expected life\>12 weeks； 4)According to RECIST1.1，there is at least one target lesion that can be stably evaluated, defining as: the longest diameter of non lymph node lesions ≥ 10 mm, or the short diameter of lymph node ≥ 15mm; 5)Sufficient vein access for monocyte collection; 6)Hematology parameters meet the following requirements: Neutrophil absolute value≥1.5×109 / L; Leukocyte≥4.0×109 / L; Hemoglobin≥80g / L; Platelets≥75×109 / L; 7) Liver function meets the following conditions: Total bilirubin≤1.5×ULN (no liver metastasis); Aspartate aminotransferase≤2.5×ULN (no liver metastasis); Alanine aminotransferase≤2.5×ULN (no liver metastasis); Alkaline phosphatase≤2.5×ULN (no liver metastasis); Total bilirubin≤2×ULN (with liver metastasis); Aspartate aminotransferase≤5.0×ULN (with liver metastasis); Alanine aminotransferase≤5.0×ULN (with liver metastasis); Alkaline phosphatase≤5.0×ULN (with liver metastasis); 8) Renal function meets the following conditions: Serum creatinine≤1.5×ULN; 9) Coagulation function meets the following conditions: International standardization ratio (INR) ≤1.5; Apart prothrombin (PTT或 APTT) ≤1.5×ULN; 10) Heart function meets the following conditions: Left ventricular ejection fraction (LVEF)≥50%; 11) The subjects can communicate well with the researchers and follow the visit, treatment, laboratory examination and other relevant regulations; 12) Female and male subjects of childbearing age agree to take effective contraceptive measures throughout the study period up to 6 months after completion of administration; 13) The subjects must give informed consent to the study before the trial and sign the written informed consent voluntarily.

You may not qualify if:

• )Serious or uncontrollable heart disease,including: Congestive heart failure with NYHA grade 3 or 4； Unstable angina beyond the control of drugs； History of myocardial infarction six months before the selection; Serious arrhythmia requiring medication; 2)Other malignant tumors occurred in the past 5 years; 3)≥ grade 3 peripheral neuropathy; 4)Patients with active infections (viruses, bacteria or fungi) requiring special treatment 5) Active hepatitis B or hepatitis C; current or past alcoholism; cirrhosis; 6)Human immunodeficiency virus ( HIV) positive; 7)According to the judgment of researchers, uncontrollable systemic diseases, including: diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, glaucoma, immune disease, pleural effusion or peritoneal effusion with symptoms requiring drainage, etc; 8)Pregnant or lactating women; 9)Baseline measurement, QTc interval, male \> 450 ms, female \> 470 ms; 10)Other unsuitable conditions judged by researchers.

Sponsors & Collaborators

• Shandong Golden Brick Biotechnology Co., Ltd.: lead

Study Sites (1)

Changguo hospital of Zibo

Zibo, China

RECRUITING

Central Study Contacts

Zhaoyong Yang, MD

CONTACT

18513385316; zhaoyongy@imb.pumc.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2020
• First Posted: May 13, 2020
• Study Start: October 8, 2019
• Primary Completion: October 8, 2021
• Study Completion: October 8, 2022
• Last Updated: May 13, 2020

Record last verified: 2020-04

Locations

CN (1)