Back to resultsA Phase I, Autologous ex Vivo Expanded and Activated NK Cell, Magicell-NK, Infusion for Colon Cancer Post Resection Study
Primary Purpose
Colon Cancer Stage I
Status
Recruiting
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
Magicell-NK contains NK cells suspended in 100 mL normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Colon Cancer Stage I
Eligibility Criteria
Inclusion Criteria:
- A dated and signed informed consent
- Either gender and aged over 20 years old (inclusive) at date of consent
- With histologically confirmed stage I or stage IIa colon cancer
- Received curative colon resection within 4~8 weeks prior to the screening visit and does not need adjuvant chemotherapy or radiotherapy
- With no ≥ grade 3 postoperative complications or has been recovered and is suitable for study enrollment according to the investigator's judgment
With adequate hematology function:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
- Total white blood cell (WBC) ≥ 3,000 cells/μL
- Platelets ≥ 100,000 counts/μL
- Hemoglobin ≥ 9 g/dL
With adequate hepatic and renal function:
- Serum creatinine ≤ 1.5 × Upper Limit of Normal (ULN)
- Total bilirubin (TB) ≤ 1.5 × ULN
- ALT and AST ≤ 2.5 × ULN
- Alkaline phosphatase (ALP) ≤ 5X ULN
- Negative response in HIV and syphilis test
- Subject with childbearing potential must agree to abstain from intercourse or use highly effective contraceptives from when signing informed consent to the Final/ET Visit.
- Performance status (ECOG) < 2
- Patients agree to be in compliant to clinical protocol planned treatment plan
Exclusion Criteria:
- Received any other investigational, anti-neoplastic medication (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only), or immune cell therapy within 28 days prior to Day 1.
- Currently under immunosuppressive or systemic steroid treatment with equivalent dosage higher than prednisolone 30 mg/day for more than 7 days within 14 days prior to Day 1
- With known tumor metastasis or coexisting malignant disease
- With ongoing acute diseases, or within the past 2 years having serious medical conditions (e.g. concomitant illness) such as cardiovascular (e.g. New York Heart Association grade III or IV), hepatic (e.g. Child-Pugh Class C), psychiatric condition (e.g. alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that, judged by the investigator, could interfere with the results of the trial or adversely affect the safety of the subject
- Known hypersensitivity to aminoglycoside or bacitracin (e.g. Streptomycin, Gentamicin)
- Known hypersensitivity to any of the components of Magicell-NK, including human serum albumin
- Female subject who is lactating or has positive urine pregnancy test at screening
Sites / Locations
- Chang Gung Memorial Hospital, LinkouRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Magicell-NK
Arm Description
Magicell-NK Cohort 1: 2 x 108 cells x 6 infusions Cohort 2: 6 x 108 cells x 6 infusions Cohort 3: 18 x 108 cells x 6 infusions
Outcomes
Primary Outcome Measures
Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs)
Number of participants with serious adverse events and treatment emergent adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) to assess tolerability of Magicell-NK treatment. Evaluation of side effects conducted during the study period. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Number of Participants With at Least One Dose Limiting Toxicity
Dose Limiting Toxicity (DLT) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 as treatment-related any greater or equal to Grade 4 adverse event of hematologic toxicity, or any greater or equal to Grade 3 adverse event of non-hematologic toxicity during Visit 3~ visit 10. With the exception of (1) fever grade 3 or grade 4 which is controllable by antihistamine and resolves to grade 2 or less within 48 hours, (2) hypersensitivity reactions occurring within 2 hours of infusion finished (related to cell infusion) that are reversible to a grade 2 or less within 48 hours with standard therapy, (3) grade 3 electrolyte imbalance or dehydration that resolves to grade 1 or less within 48 hours, (4) grade 3 nausea, vomiting, or diarrhea which is controllable by standard medication that resolves to grade 1 or less within 48 hours, (5) fatigue which resolves to grade 1 or less within 7 days.
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
MTD is defined as the highest dose level at which ≤ 1/6 of subjects experiences DLT during Visit 3~10, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design. Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of therapy was determined by monitoring dose-limiting toxicity and adverse events in the dosing cohorts
Secondary Outcome Measures
Disease free survival (DFS)
The time from the date of the first Magicell-NK infusion to the date of the first disease-free survival event (recurrence, second primary colon cancer or death from any cause).
Changes in Frequency and Duration of ctDNA
Number of participants experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any Magicell-NK regimen remaining disease free. Change in values will be tabulated descriptively by visit with 95% two-sided confidence interval.
Changes in Frequency and Duration of Circulating Tumor Count (CTC) and Programmed Death-Ligand 1 Circulating Tumor Count (PD-L1+ CTC) counts
Determine the effect of Magicell-NK on reducing CTC and PD-L1+ CTC of whole blood in colon cancer with elevated baseline CTC count and PD-L1+ CTC to identify the least effective dose that clears CTCs and PD-L1+ CTC. Baseline count of CTC and PD-L1+ CTC will be recorded prior to before Magicell-NK therapy in a whole blood sample. Count of CTC and PD-L1+ CTC will be measured at 1 week (post treatment evaluation visit), and 10-12 weeks (follow up visits) after Magicell-NK therapy in a whole blood sample. These values will be compared.
Changes in Biomarkers (CEA and CA19-9)
Determine the effect of Magicell-NK on CEA and CA 19-9 in colon cancer with elevated baseline CEA and CA 19-9 to identify the least effective dose that clears CEA and CA 19-9. Baseline count of CEA and CA 19-9 will be recorded prior to before Magicell-NK therapy. Count of CEA and CA 19-9 will be measured at 1 week (post treatment evaluation visit), and 10-12 weeks (follow up visits) after Magicell-NK therapy. These values will be compared.
Full Information
NCT ID
NCT05394714
First Posted
May 11, 2022
Last Updated
July 11, 2023
Sponsor
Medigen Biotechnology Corporation
1. Study Identification
Unique Protocol Identification Number
NCT05394714
Brief Title
A Phase I, Autologous ex Vivo Expanded and Activated NK Cell, Magicell-NK, Infusion for Colon Cancer Post Resection Study
Official Title
A Dose-Escalating Phase I Study to Determine the Safety, and Maximum Tolerated Dose/ Maximum Feasible Dose of Autologous ex Vivo Expanded and Activated NK Cell, Magicell-NK, Infusion for Colon Cancer Post Resection
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medigen Biotechnology Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase I, open-label study to explore the safety profile and to find the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of Magicell-NK in subjects diagnosed with stage I or stage IIa colon cancer post resection from a single site in Taiwan.
During this study, 3 dose levels of Magicell-NK will be tested with a 3+3 design to determine the MTD/MFD: Cohort 1, low dose (2×108 cells), Cohort 2, middle dose (6×108 cells), and Cohort 3, high dose (18 ×108 cells).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer Stage I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Magicell-NK
Arm Type
Experimental
Arm Description
Magicell-NK Cohort 1: 2 x 108 cells x 6 infusions Cohort 2: 6 x 108 cells x 6 infusions Cohort 3: 18 x 108 cells x 6 infusions
Intervention Type
Biological
Intervention Name(s)
Magicell-NK contains NK cells suspended in 100 mL normal saline
Intervention Description
Eligible subjects will be assigned into one of the three dose escalating cohorts (3+3 subjects/cohort) according to the time sequence enrolled
Primary Outcome Measure Information:
Title
Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs)
Description
Number of participants with serious adverse events and treatment emergent adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) to assess tolerability of Magicell-NK treatment. Evaluation of side effects conducted during the study period. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame
Up to 60 weeks
Title
Number of Participants With at Least One Dose Limiting Toxicity
Description
Dose Limiting Toxicity (DLT) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 as treatment-related any greater or equal to Grade 4 adverse event of hematologic toxicity, or any greater or equal to Grade 3 adverse event of non-hematologic toxicity during Visit 3~ visit 10. With the exception of (1) fever grade 3 or grade 4 which is controllable by antihistamine and resolves to grade 2 or less within 48 hours, (2) hypersensitivity reactions occurring within 2 hours of infusion finished (related to cell infusion) that are reversible to a grade 2 or less within 48 hours with standard therapy, (3) grade 3 electrolyte imbalance or dehydration that resolves to grade 1 or less within 48 hours, (4) grade 3 nausea, vomiting, or diarrhea which is controllable by standard medication that resolves to grade 1 or less within 48 hours, (5) fatigue which resolves to grade 1 or less within 7 days.
Time Frame
Within 14-day observation of the first treatment. up to 60 weeks
Title
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
Description
MTD is defined as the highest dose level at which ≤ 1/6 of subjects experiences DLT during Visit 3~10, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design. Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of therapy was determined by monitoring dose-limiting toxicity and adverse events in the dosing cohorts
Time Frame
3 weeks from start of treatment, up to 60 weeks
Secondary Outcome Measure Information:
Title
Disease free survival (DFS)
Description
The time from the date of the first Magicell-NK infusion to the date of the first disease-free survival event (recurrence, second primary colon cancer or death from any cause).
Time Frame
Up to 60 weeks
Title
Changes in Frequency and Duration of ctDNA
Description
Number of participants experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any Magicell-NK regimen remaining disease free. Change in values will be tabulated descriptively by visit with 95% two-sided confidence interval.
Time Frame
Up to 60 weeks
Title
Changes in Frequency and Duration of Circulating Tumor Count (CTC) and Programmed Death-Ligand 1 Circulating Tumor Count (PD-L1+ CTC) counts
Description
Determine the effect of Magicell-NK on reducing CTC and PD-L1+ CTC of whole blood in colon cancer with elevated baseline CTC count and PD-L1+ CTC to identify the least effective dose that clears CTCs and PD-L1+ CTC. Baseline count of CTC and PD-L1+ CTC will be recorded prior to before Magicell-NK therapy in a whole blood sample. Count of CTC and PD-L1+ CTC will be measured at 1 week (post treatment evaluation visit), and 10-12 weeks (follow up visits) after Magicell-NK therapy in a whole blood sample. These values will be compared.
Time Frame
Up to 60 weeks
Title
Changes in Biomarkers (CEA and CA19-9)
Description
Determine the effect of Magicell-NK on CEA and CA 19-9 in colon cancer with elevated baseline CEA and CA 19-9 to identify the least effective dose that clears CEA and CA 19-9. Baseline count of CEA and CA 19-9 will be recorded prior to before Magicell-NK therapy. Count of CEA and CA 19-9 will be measured at 1 week (post treatment evaluation visit), and 10-12 weeks (follow up visits) after Magicell-NK therapy. These values will be compared.
Time Frame
Up to 60 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A dated and signed informed consent
Either gender and aged over 20 years old (inclusive) at date of consent
With histologically confirmed stage I or stage IIa colon cancer
Received curative colon resection within 4~8 weeks prior to the screening visit and does not need adjuvant chemotherapy or radiotherapy
With no ≥ grade 3 postoperative complications or has been recovered and is suitable for study enrollment according to the investigator's judgment
With adequate hematology function:
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
Total white blood cell (WBC) ≥ 3,000 cells/μL
Platelets ≥ 100,000 counts/μL
Hemoglobin ≥ 9 g/dL
With adequate hepatic and renal function:
Serum creatinine ≤ 1.5 × Upper Limit of Normal (ULN)
Total bilirubin (TB) ≤ 1.5 × ULN
ALT and AST ≤ 2.5 × ULN
Alkaline phosphatase (ALP) ≤ 5X ULN
Negative response in HIV and syphilis test
Subject with childbearing potential must agree to abstain from intercourse or use highly effective contraceptives from when signing informed consent to the Final/ET Visit.
Performance status (ECOG) < 2
Patients agree to be in compliant to clinical protocol planned treatment plan
Exclusion Criteria:
Received any other investigational, anti-neoplastic medication (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only), or immune cell therapy within 28 days prior to Day 1.
Currently under immunosuppressive or systemic steroid treatment with equivalent dosage higher than prednisolone 30 mg/day for more than 7 days within 14 days prior to Day 1
With known tumor metastasis or coexisting malignant disease
With ongoing acute diseases, or within the past 2 years having serious medical conditions (e.g. concomitant illness) such as cardiovascular (e.g. New York Heart Association grade III or IV), hepatic (e.g. Child-Pugh Class C), psychiatric condition (e.g. alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that, judged by the investigator, could interfere with the results of the trial or adversely affect the safety of the subject
Known hypersensitivity to aminoglycoside or bacitracin (e.g. Streptomycin, Gentamicin)
Known hypersensitivity to any of the components of Magicell-NK, including human serum albumin
Female subject who is lactating or has positive urine pregnancy test at screening
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jude Chen
Phone
886-2-77361234
Ext
610
Email
jude@medigen.com.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Chiachien Lee
Phone
886-2-77361234
Ext
690
Email
chiachien.lee@medigen.com.tw
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stanley Chang, PhD
Organizational Affiliation
Medigen Biotechnology Corporation
Official's Role
Study Chair
Facility Information:
Facility Name
Chang Gung Memorial Hospital, Linkou
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chun Kai Liao, M.D.
Phone
886-3-3281200
Ext
2101
Email
mr9023@cgmh.org.tw
First Name & Middle Initial & Last Name & Degree
Chun Kai Liao, M.D.
First Name & Middle Initial & Last Name & Degree
Chien Yuh Yeh, M.D.
First Name & Middle Initial & Last Name & Degree
Jinn Shiun Chen, M.D.
First Name & Middle Initial & Last Name & Degree
Pao Shiu Hsieh, M.D.
First Name & Middle Initial & Last Name & Degree
Jeng Fu You, M.D.
First Name & Middle Initial & Last Name & Degree
Geng Pin Lin, PhD
First Name & Middle Initial & Last Name & Degree
An Hsin Chen, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase I, Autologous ex Vivo Expanded and Activated NK Cell, Magicell-NK, Infusion for Colon Cancer Post Resection Study
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