Umbilical Cord Blood Derived MAK Immune Cells Combined With Standard Second-Line Treatments for Hepatobiliary and Pancreatic Malignancies

Clinical Study on the Safety and Efficacy of Umbilical Cord Blood Derived MAK Immune Cells Combined With Standard Second-Line Treatments for Hepatobiliary and Pancreatic Malignancies：HCCSC AB04 Trial

To evaluate the safety of MAK immune cells derived from umbilical cord blood combined with second-line treatments for hepatobiliary and pancreatic malignancies.And to investigate the initial efficacy of MAK immune cells derived from umbilical cord blood combined with second-line treatments for hepatobiliary and pancreatic malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IV Pancreatic Cancer; Hepatocellular Carcinoma , Cholangiocarcinoma
• Intervention / Treatment: Biological: Umbilical Cord Blood Derived MAK Immune Cells

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fuxiang Zhou; Phone Number: +86-027-67813155; Email: happyzhoufx@sina.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age over 18 years old, under 75 years old, men and women;
2. Subjects participated voluntarily, gave full informed consent, signed a written informed consent, with good compliance;
3. Hepatocytic carcinoma or biliary or pancreatic-derived adenocarcinoma was clearly diagnosed by histological or cytology pathology;
4. Recurrent hepatobiliary or pancreatic malignancies with unresectable advanced or metastatic, or postoperative adjuvant therapy (chemotherapy and / or radiation therapy) for 12 months, with a Child-Pugh score of 7;
5. With 1 measurable lesion, according to the RECIST v 1.1 criteria.Requirements: The selected target lesion has not previously received local treatment, or the selected target lesion was located in the previous local treatment area after passing the imaging examination and was determined as PD according to the RECIST v 1.1 criteria;
6. ECOG score of 0-1;
7. Expected survival is greater than 3 months;

8. Main organ function composite with the following requirements:

   • Absolute neutrophil count was 1.5*10^9 / L;
   • Platelet count was 75*10^9 / L;
   • Hemoglobin was at 90g / L;
   • Serum albumin at 30g / L;
   • Serum bilirubin 1.5 upper Range normal limit (ULN);
   • Altraverine aminotransferase (ALT), aspartate aminotransferase (AST) 2.5 upper normal range limit (ULN);
   • Serum creatinine (Cr) 1.5 Upper Limit of normal range (ULN) or Cr clearance of 40 mL/min;
   • The International standardized ratio (INR) 2 or Prothrombin Time (PT) exceeds the upper limit of the normal range for 6 seconds;

   • Urinary protein <2 + (if urine protein 2 +, 24 h (h), and 24h <1.0g can be enrolled).

     9.If HBsAg (+) and / or HBcAb (+), HBV DNA must be <500IU / mL and during the study period, the original anti-HBV treatment continues throughout the study, or start entecavir or teenofavir.

     10.There is no previous history of abdominal radiotherapy. If radiation has been performed, the complete target area scope and treatment plan are more than 2 weeks apart from the study immune cell transfusion of this project; 11.No history of organ transplantation; 12.Women of childbearing age performed a serum pregnancy test within 7 days before the initiation of treatment, and agreed to adopt a reliable and effective contraceptive method during the trial and within 60 days after the final administration of the test drug.For male subjects with a partner of women of childbearing age, consent was given to a reliable and effective approach to contraception during the trial and within 60 days after the final administration of the test medication.

Exclusion Criteria:

1. At the same time, there are serious medical diseases, including serious heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled infection, active digestive tract ulcer;
2. Patients with brain metastasis with clinical symptoms;
3. Suffering from other primary malignancies in the past 5 years (except skin BCC or squamous cell carcinoma, cervical carcinoma in situ that have been effectively controlled);
4. Patients with immunodeficiency or autoimmune diseases (e. g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, insulin-dependent diabetes, etc.).
5. Patients who participated in other clinical trials or clinical study treatment within the 3 months prior to this clinical study.
6. Patients treated with other cells within the last 6 months.
7. Patients with infection and fever who were not effectively controlled.
8. Patients with high allergies or a history of severe allergies.
9. Patients with an albumin allergy.
10. Patients after organ transplantation; patients with long-term use or who are using immunosuppressants.
11. Patients with severe other organ dysfunction.
12. Patients with organ bleeding, severe hypertension, and patients with a cardiac pacemaker.
13. Women during pregnancy or lactation; or women of childbearing age have positive blood pregnancy, women of childbearing age and their spouses are unwilling to take effective contraception during the clinical study and within 6 months of the end.
14. Patients who are not considered appropriate to participate in this clinical study (e. g., poor compliance, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Umbilical Cord Blood Derived MAK Immune Cells	Biological: Umbilical Cord Blood Derived MAK Immune Cells; Intravenous drip; Other Names: Second-line standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival(PFS)	PFS is defined as the time from enrollment to the first documented disea	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	OS is the time from enrollment to death due to any cause.	24 months
objective response rate (ORR)	and partial response (PR) by the investigator according to the RECIST 1.1.	24 months
disease control rate (DCR)	DCR was defined as the percentage of participants who have a confirmed complete response（CR） or partial response（PR） or stable disease（SD） per RECIST 1.1 as assessed by investigator	24 months

Collaborators and Investigators

• Sponsor: Zhou Fuxiang

Study record dates

Study Major Dates

• Study Start (Anticipated): February 7, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: February 4, 2022
• First Submitted That Met QC Criteria: February 4, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: HCCSC AB04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No