Study on the Safety and Effectiveness of UCB-NK Cell Infusion in the Treatment of Advanced Gastric Cancer and Gastroesophageal Cancer
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|ClinicalTrials.gov Identifier: NCT04385641|
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : May 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Gastric Cancer Gastroesophageal Cancer||Other: Cell infusion for Dose-finding (Group A) Other: Cell infusion for Extended research (Group B)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Study on the Safety and Effectiveness of UCB-NK Cell Infusion in the Treatment of Advanced Gastric Cancer and Gastroesophageal Cancer|
|Actual Study Start Date :||October 8, 2019|
|Estimated Primary Completion Date :||October 8, 2021|
|Estimated Study Completion Date :||October 8, 2022|
Experimental: Dose-finding (Group A)
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)
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.
Experimental: Extended research (Group B)
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)
Group B：Non myeloablative immunosuppressive pretreatment and cell transfusion were the same as group A.
- Safety assessment [ Time Frame: 4 weeks ]Evaluation of adverse events and severity according to CTCAE v5.0
- Hematology toxicity [ Time Frame: 7 days ]After 7 days of treatment, the ≥ 4 degree hematotoxicity (excluding lymphocyte reduction) related to UCB-NK treatment could not recover to ≤ 3 degree
- Non hematologic toxicity [ Time Frame: 7 days ]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.
- Tumor assessment [ Time Frame: 4 years ]
Imaging of the chest, abdomen and pelvis (either enhanced CT or MRI) and tumor markers should be obtained at baseline (before the pretreatment of first lymphocyte clearance)， this imaging evaluation is the baseline examination of this study. After the infusion, patients need to return to the hospital at the 1st, 2nd, 3rd, 4th, 6th and 12th month (± 7 days) and every 6 months (± 1 month) after the 12th month to check the imaging of chest, abdomen and pelvis and tumor markers. Follow up to the disease progress, unwilling to be followed up, loss of follow-up, death or the end of the study, whichever occurs first.
Imaging evaluation is up to the established disease progression (PD) according to the RECIST 1.1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04385641
|Contact: Zhaoyong Yang, MDfirstname.lastname@example.org|
|Changguo hospital of Zibo||Recruiting|