Back to resultsDendritic Killer Cell-based Immunotherapy for Solid Tumors
Primary Purpose
Colorectal Neoplasms, Hepatocellular Carcinoma, Neoplasm Metastasis
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Dendritic Killer Cell (DKC)
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring Clinical Trial, Phase I
Eligibility Criteria
Inclusion Criteria:
- Capable and willing of providing signed informed consent before study
- Patient age ≥20 at date of consent
- Performance status (ECOG) ≤2
- Patients have a life expectancy of > 3 months
- Patients agree to be in compliant to clinical protocol planned treatment plan
- Histologically confirmed metastatic solid tumor, including colon cancer, gastric cancer, pancreatic cancer, bile duct cancer, liver cancer
- Patient with histological and conventional imaging proven measurable lesion
- Patients not pregnant. All male and female patients with reproduction ability should use appropriate contraception method(s) during the study period
- Patient is not currently under immunosuppressive treatment for previous or recurred autoimmune disease
- Patient should have received and failed prior standard cancer therapies (according to TVGH standard cancer treatment procedures, or National Comprehensive Cancer Network clinical practice guidelines in oncology)
Patient with adequate hematology function:
Absolute neutrophil count (ANC) ≥ 1,500 cells Total white blood cell (WBC) ≥ 3,000 cells /mm3 Hemoglobin ≥ 9 g/dl Platelets ≥ 100,000 counts /mm3
- Patient with adequate hepatic and renal function Serum creatinine ≤ 1.5X Upper Limit of Normal (ULN) Total bilirubin (TB) ≤ 1.5X ULN, or ≤ 2.5X ULN for patients with primary HCC or liver metastasis ALT and AST ≤ 2.5X ULN, or ≤ 5X ULN for patients with primary HCC or liver metastasis Alkaline phosphatase (ALP) ≤ 5X ULN
- Patient showing negative response in syphilis, HIV, HBV and HCV test
Exclusion Criteria:
- Any other investigational drug used within 28 days prior to first DKC administration
- Patient with known brain metastasis or metastasis to central nervous system
- Patient with pulmonary fibrosis
- Patient with pleural effusion or as cites correspond to CTCAE grading > 2
- Patient with uncontrolled disease including but not limit to cardiovascular disease, liver disease, renal disease or infectious disease
- Patients being diagnosed with any cognitive or psychiatric illness
- Patient not suitable to participate the trial for safety concerns as judged by the investigator
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dendritic Killer Cell (DKC)
Arm Description
All enrolled patients received one treatment cycle of DKC cell therapy, which consists of 5 infusion cycles approximately 23 days apart. There were 3 dose levels: 5 x 10^6, 1 x 10^7, and 5 x 10^7 cells, and the protocol followed a traditional 3+3 dose escalation design.
Outcomes
Primary Outcome Measures
Safety of DKC as assessed by adverse event (AE)
The coding system used for AE is MedDRA. Only treatment-emergent adverse events (TEAEs) are considered for primary endpoint. Frequency table of subjects with pre-treatment and treatment-emergent AE are presented by each cohort and overall trial. AE incidents are summarized descriptively by system organ class and preferred term using MedDRA for each cohort and overall trial.
Safety of DKC as assessed by serious adverse event (SAE)
Serious adverse event incidence is summarized descriptively by system organ class and preferred term for each cohort and overall trial. The causality of SAEs will be assessed by the principal investigator for its relationship to study medication.
Safety of DKC as assessed by dose-limiting toxicity (DLT)
DLT is defined as Grade ≧ 3 (according to NCI-CTCAE 4.03 grading system), study medication-related (i.e. with causality determined as at least possibly related to study medication), and worsened in comparison to baseline (pre-treatment condition). DLT is determined after first infusion cycle and maximum tolerated dose (MTD) is determined as the highest dose without DLT. DLT is defined by the items listed below:
Blood and lymphatic system disorders: Grade ≧ 3 of (1) Any febrile neutropenia, (2) Leukocytosis, (3) Anemia
Other disorders: Grade ≧ 3 of (1) Diarrhea, (2) Vomiting, (3) Fever, (4) Nausea, (5) Anaphylaxis
Safety of DKC as assessed by combining with concomitant anticancer treatment
The subjects enrolled in the study are cancer patients, who were treated with anticancer drugs before, and possibly during, DKC immunotherapy. Potential adverse drug-drug interaction (DDI) is monitored during treatment and follow-up period.
Safety of DKC as assessed by laboratory examinations
For each cohort, there are 5 baselines (taken 9 days before infusion) for 5 infusion cycles, and there are 2 evaluation time points in each infusion cycle (at end of first week and second week after infusion) and 4 in the follow-up period (at every 12 weeks). The laboratory evaluation results are tabulated in two aspects: 1) the percentage changes between each evaluation and corresponding baselines, and 2) the mean baseline values of each cycle in each cohort. Laboratory results regarding different functional categories are described separately in following areas.
Hematology related items: Hb (g/dL), WBC (count/uL), Platelet (x 10^3 count/uL), ANC (count/uL)
Liver function related items: C-RP (mg/dL), Glucose AC (mg/dL), Total Bilirubin (mg/dL), AST (U/L), ALT (U/L), LDH (U/L), ALP (U/L), gammaGT (U/L)
Serum lipids and proteins, renal function, and electrolytes related items: HDL-C (mg/dL), Total Cholesterol (mg/dL), Triglyceride (mg/dL), Creatinine (mg/dL), BUN (mg/dL)
Secondary Outcome Measures
Efficacy of DKC as assessed by tumor specific T cell response
The tumor specific T cell response was assessed by the detection of CD3+CD8+CD69+IFN-gamma+ T lymphocytes in percentage relative to total peripheral blood mononuclear cells (PBMCs). Baseline value was measured before first infusion cycle, and subsequent evaluation time points were measured right after infusion cycles 2, 3, and 4.
Efficacy of DKC as assessed by change in quality of life
The quality of life as assessed by the WHO QoL-BREF questionnaire, and the transformed scores (0-100) was used to facilitate the interpretation. Baseline value was measured before first infusion cycle, and evaluation time points were taken right after infusion cycles 2, 3, 4, and 5. During the follow-up period, evaluation time points were taken at every 12 weeks for a total of 4 time points.
Full Information
NCT ID
NCT02882659
First Posted
August 18, 2016
Last Updated
August 24, 2016
Sponsor
FullHope Biomedical Co., Ltd.
Collaborators
Taipei Veterans General Hospital, Taiwan
1. Study Identification
Unique Protocol Identification Number
NCT02882659
Brief Title
Dendritic Killer Cell-based Immunotherapy for Solid Tumors
Official Title
Phase I Clinical Trial of Autologous Dendritic Killer Cell-based Immunotherapy for Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FullHope Biomedical Co., Ltd.
Collaborators
Taipei Veterans General Hospital, Taiwan
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the safety of autologous dendritic killer cell (DKC) in patients with metastatic solid tumor and to evaluate the maximum tolerated dose (MTD) of DKC. The primary endpoint of safety evaluation includes physical examination, assessment of vital sign, laboratory test, concomitant medication, and adverse event (AE). The secondary endpoints regarding efficacy includes the generation of tumor specific immune response by detecting CD3+ CD8+ CD69+ IFN-gamma+ T cells, and the improvement of quality of life
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms, Hepatocellular Carcinoma, Neoplasm Metastasis
Keywords
Clinical Trial, Phase I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dendritic Killer Cell (DKC)
Arm Type
Experimental
Arm Description
All enrolled patients received one treatment cycle of DKC cell therapy, which consists of 5 infusion cycles approximately 23 days apart. There were 3 dose levels: 5 x 10^6, 1 x 10^7, and 5 x 10^7 cells, and the protocol followed a traditional 3+3 dose escalation design.
Intervention Type
Biological
Intervention Name(s)
Dendritic Killer Cell (DKC)
Other Intervention Name(s)
FullHope Cell Therapy A (FHCTA)
Intervention Description
DKC is a hybrid cell type capable of dual functionality, i.e. cytotoxicity and antigen presentation, similar to NK cells and DCs, respectively.
Primary Outcome Measure Information:
Title
Safety of DKC as assessed by adverse event (AE)
Description
The coding system used for AE is MedDRA. Only treatment-emergent adverse events (TEAEs) are considered for primary endpoint. Frequency table of subjects with pre-treatment and treatment-emergent AE are presented by each cohort and overall trial. AE incidents are summarized descriptively by system organ class and preferred term using MedDRA for each cohort and overall trial.
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
Title
Safety of DKC as assessed by serious adverse event (SAE)
Description
Serious adverse event incidence is summarized descriptively by system organ class and preferred term for each cohort and overall trial. The causality of SAEs will be assessed by the principal investigator for its relationship to study medication.
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
Title
Safety of DKC as assessed by dose-limiting toxicity (DLT)
Description
DLT is defined as Grade ≧ 3 (according to NCI-CTCAE 4.03 grading system), study medication-related (i.e. with causality determined as at least possibly related to study medication), and worsened in comparison to baseline (pre-treatment condition). DLT is determined after first infusion cycle and maximum tolerated dose (MTD) is determined as the highest dose without DLT. DLT is defined by the items listed below:
Blood and lymphatic system disorders: Grade ≧ 3 of (1) Any febrile neutropenia, (2) Leukocytosis, (3) Anemia
Other disorders: Grade ≧ 3 of (1) Diarrhea, (2) Vomiting, (3) Fever, (4) Nausea, (5) Anaphylaxis
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
Title
Safety of DKC as assessed by combining with concomitant anticancer treatment
Description
The subjects enrolled in the study are cancer patients, who were treated with anticancer drugs before, and possibly during, DKC immunotherapy. Potential adverse drug-drug interaction (DDI) is monitored during treatment and follow-up period.
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
Title
Safety of DKC as assessed by laboratory examinations
Description
For each cohort, there are 5 baselines (taken 9 days before infusion) for 5 infusion cycles, and there are 2 evaluation time points in each infusion cycle (at end of first week and second week after infusion) and 4 in the follow-up period (at every 12 weeks). The laboratory evaluation results are tabulated in two aspects: 1) the percentage changes between each evaluation and corresponding baselines, and 2) the mean baseline values of each cycle in each cohort. Laboratory results regarding different functional categories are described separately in following areas.
Hematology related items: Hb (g/dL), WBC (count/uL), Platelet (x 10^3 count/uL), ANC (count/uL)
Liver function related items: C-RP (mg/dL), Glucose AC (mg/dL), Total Bilirubin (mg/dL), AST (U/L), ALT (U/L), LDH (U/L), ALP (U/L), gammaGT (U/L)
Serum lipids and proteins, renal function, and electrolytes related items: HDL-C (mg/dL), Total Cholesterol (mg/dL), Triglyceride (mg/dL), Creatinine (mg/dL), BUN (mg/dL)
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
Secondary Outcome Measure Information:
Title
Efficacy of DKC as assessed by tumor specific T cell response
Description
The tumor specific T cell response was assessed by the detection of CD3+CD8+CD69+IFN-gamma+ T lymphocytes in percentage relative to total peripheral blood mononuclear cells (PBMCs). Baseline value was measured before first infusion cycle, and subsequent evaluation time points were measured right after infusion cycles 2, 3, and 4.
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days)
Title
Efficacy of DKC as assessed by change in quality of life
Description
The quality of life as assessed by the WHO QoL-BREF questionnaire, and the transformed scores (0-100) was used to facilitate the interpretation. Baseline value was measured before first infusion cycle, and evaluation time points were taken right after infusion cycles 2, 3, 4, and 5. During the follow-up period, evaluation time points were taken at every 12 weeks for a total of 4 time points.
Time Frame
Entire treatment period (cycle 1-5, 116 +/- 4 days) and follow-up period (452 +/- 4 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Capable and willing of providing signed informed consent before study
Patient age ≥20 at date of consent
Performance status (ECOG) ≤2
Patients have a life expectancy of > 3 months
Patients agree to be in compliant to clinical protocol planned treatment plan
Histologically confirmed metastatic solid tumor, including colon cancer, gastric cancer, pancreatic cancer, bile duct cancer, liver cancer
Patient with histological and conventional imaging proven measurable lesion
Patients not pregnant. All male and female patients with reproduction ability should use appropriate contraception method(s) during the study period
Patient is not currently under immunosuppressive treatment for previous or recurred autoimmune disease
Patient should have received and failed prior standard cancer therapies (according to TVGH standard cancer treatment procedures, or National Comprehensive Cancer Network clinical practice guidelines in oncology)
Patient with adequate hematology function:
Absolute neutrophil count (ANC) ≥ 1,500 cells Total white blood cell (WBC) ≥ 3,000 cells /mm3 Hemoglobin ≥ 9 g/dl Platelets ≥ 100,000 counts /mm3
Patient with adequate hepatic and renal function Serum creatinine ≤ 1.5X Upper Limit of Normal (ULN) Total bilirubin (TB) ≤ 1.5X ULN, or ≤ 2.5X ULN for patients with primary HCC or liver metastasis ALT and AST ≤ 2.5X ULN, or ≤ 5X ULN for patients with primary HCC or liver metastasis Alkaline phosphatase (ALP) ≤ 5X ULN
Patient showing negative response in syphilis, HIV, HBV and HCV test
Exclusion Criteria:
Any other investigational drug used within 28 days prior to first DKC administration
Patient with known brain metastasis or metastasis to central nervous system
Patient with pulmonary fibrosis
Patient with pleural effusion or as cites correspond to CTCAE grading > 2
Patient with uncontrolled disease including but not limit to cardiovascular disease, liver disease, renal disease or infectious disease
Patients being diagnosed with any cognitive or psychiatric illness
Patient not suitable to participate the trial for safety concerns as judged by the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yee Chou, M.D., Ph.D.
Organizational Affiliation
Taipei Veteran General Hospital, Taiwan R.O.C.
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Dendritic Killer Cell-based Immunotherapy for Solid Tumors
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