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Safety Study of Adoptive Transfer of Autologous IKDC-like Cells

Sponsor
National Defense Medical Center, Taiwan (Other)
Overall Status
Completed
CT.gov ID
NCT02661685
Collaborator
Ministry of Science and Technology, Taiwan (Other), Academia Sinica, Taiwan (Other)
6
Enrollment
1
Location
1
Arm
41
Actual Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety of adoptive transferring autologous IKDC-like cells

Condition or Disease Intervention/Treatment Phase
  • Biological: autologous IKDC-like cells
 Phase 1

Detailed Description

Cancer immunosurveillance in mice and human protects the host from outgrowth of tumor cells. This may establish a sufficient rationale for cancer immunotherapy that aims to control or eradicate tumor by an induction of effective anti-tumor immunity. The interest in developing cancer immunotherapy has intensified by the recent trials results showing durable responses in approximately 20% of patients who received various kinds of immunotherapy including adoptive transfer of tumor-specific T cells, cancer vaccines, and T cell response checkpoint blockade inhibition. Discoveries to date, natural killer (NK) cell function positively associates with reduction of cancer risk and with better survival of gastrointestinal stromal tumor patients. Interferon-producing killer dendritic cells (IKDCs) are a subpopulation of NK cells discovered in the mouse spleen, which can lyse tumor cells and acquire antigen presentation cell (APC) activity. We found putative IKDCs in human peripheral blood mononuclear cells (PBMCs); meanwhile, we also developed a method to expand IKDC-like cells from murine bone marrow and human PBMC ex vivo. The expanded human IKDC-like cells are cytotoxic toward several human leukemia cell lines and are capable to activate allogeneic T cells. For the in vivo anti-tumor activity, we found that two transfers of syngeneic murine IKDC-like cells reduced tumor burden in B16/OVA and B16/F10 melanoma and Lewis lung carcinoma models, and enhanced interferon (IFN)-γ production by the splenocytes of the tumor-bearing mice. Moreover, six transfers of IKDC-like cell significantly prolonged the survival of mice bearing B16/F10 melanoma. Based on these preclinical results, we hypothesize anti-tumor activity of human IKDC-like cells. We thus propose a phase 1 clinical trial to assess the safety of autologous IKDC-like cell therapy in metastatic cancer patients for determination of the maximum tolerated dose, and to monitor the immune parameters in patients before and after the IKDC-like cell transfer to investigate the therapeutic mechanism and biomarkers.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
3+3 statistics model3+3 statistics model
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Immunotherapy for Metastatic Cancer Patients by Adoptive Transfer of Autologous IKDC-like Cells - Phase 1 Clinical Trial
Actual Study Start Date :
May 1, 2016
Actual Primary Completion Date :
Oct 1, 2019
Actual Study Completion Date :
Oct 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: autologous IKDC-like cell

Received autologous IKDC-like cells

Biological: autologous IKDC-like cells
Subject received autologous IKDC-like cells every 14 days

Outcome Measures

Primary Outcome Measures

  1. Evaluation of subject with Grade 3 or above adverse events that received autologous IKDC-like cells, graded according to NCI-CTCAE v4.03 [Through study complete, an average about 1.5 years]

    I. Safety is evaluated by assessment of does-limiting toxicity (DLT) according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 or above. II. DLT is defined as follows: Any Grade 3 or above toxicity regarding general disorders or immune disorders defined by NCI-CTCAE is determined by the investigator to be possibly related in causality to the treatment. Fever, chillness, flu-like symptoms, or infusion-related reactions of grade 3 or more are to be counted as DLT only if they remain at grade 3 or more for more than three days despite of adequate symptomatic medications.. III. The maximum tolerated dose (MTD) of autologous IKDC-like cell will be determined via a 3+3 traditional design.

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Histologically confirmed metastatic/recurrent non-hematological cancer, stage IV at study entry.

  • Age: 21-75 years.

  • ECOG performance status 0-1.

  • Patients must have at least one measurable lesion.

  • Patients' disease must have failed at least one-line of standard chemotherapy/targeted therapy or other treatment in the metastatic setting.

  • Patients' estimated life expectancy is more than 3 months.

  • Patients who refuse chemotherapy, or who are physiologically unsuitable for chemotherapy or any other standard therapy per investigator's discretion will be considered eligible for this trial.

  • Patients must have adequate bone marrow function, defined as WBC ≥ 3500/mm3, neutrophil ≥ 1500/mm3, lymphocyte ≥ 1,000/mm3, and platelet ≥ 100,000/mm3.

  • Patients must have adequate liver and renal function, defined as serum alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 5 times normal, bilirubin ≤ 1.5 times normal range, and creatinine ≤ 1.5 times upper normal limit.

  • All patients should have documentation of negative result of penicillin test.

  • Women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent.

Exclusion Criteria:

  • Subjects with metastatic cancer in disease progression (expected survival time < 3 months).

  • Subjects who have had chemotherapy less than 4 weeks before the start of trial.

  • Subjects who received IFN-γ or GM-CSF less than 4 weeks before the start of trial.

  • Subjects who are HIV, HBV, or HCV positive.

  • Patients who have central nervous system metastasis except for those whose CNS disease have been treated with radiotherapy (Disease-free > 6 months) and/or surgery and have been stable for at least two weeks.

  • Patients who have active acute or chronic infection (at the discretion of the investigator).

  • Pregnant or breast-nursing women.

  • Patients who have active cardiac disease requiring therapy for failure, angina, arrhythmia, or infarction within the preceding 6 months (exception: any patient whose cardiac failure is compensated on medications).

  • Subjects who have received corticosteroids or other immunosuppressive agents less than 4 weeks before starting trial.

  • Subjects who have asthma and/or are on treatment for asthma.

  • Subjects with history of autoimmune disease, such as lupus, multiple sclerosis, Ankylosing Spondylitis, Systemic Sclerosis.

  • Subjects with a history of other systemic disease..

  • History of neoplastic disease within the last 5 years except for carcinoma in situ of the cervix, superficial bladder cancer or basal/squamous cell carcinoma of the skin.

  • Subjects who present with open wounds.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tri-Service General Hospital Taipei Taiwan 114

Sponsors and Collaborators

  • National Defense Medical Center, Taiwan
  • Ministry of Science and Technology, Taiwan
  • Academia Sinica, Taiwan

Investigators

  • Principal Investigator: Ming-Shen Dai, MD/PhD, Attending Physician

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ming-Shen Dai, Attending physician, National Defense Medical Center, Taiwan
ClinicalTrials.gov Identifier:
NCT02661685
Other Study ID Numbers:
  • IKDC-001
First Posted:
Jan 22, 2016
Last Update Posted:
Feb 18, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Ming-Shen Dai, Attending physician, National Defense Medical Center, Taiwan
Cancer immunotherapy
IFN-γ-producing killer dendritic cell-like cells
Natural killer cells
Additional relevant MeSH terms:
Neoplasm Metastasis

Study Results

No Results Posted as of Feb 18, 2021