Safety Study of Adoptive Transfer of Autologous IKDC-like Cells

February 17, 2021 updated by: Ming-Shen Dai, National Defense Medical Center, Taiwan

An Immunotherapy for Metastatic Cancer Patients by Adoptive Transfer of Autologous IKDC-like Cells - Phase 1 Clinical Trial

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 114
        • Tri-Service General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of subject with Grade 3 or above adverse events that received autologous IKDC-like cells, graded according to NCI-CTCAE v4.03
Time Frame: 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.
Through study complete, an average about 1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Defense Medical Center, Taiwan

Collaborators

Ministry of Science and Technology, Taiwan
Academia Sinica, Taiwan

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2016

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

October 1, 2019

Study Registration Dates

First Submitted

January 13, 2016

First Submitted That Met QC Criteria

January 19, 2016

First Posted (Estimate)

January 22, 2016

Study Record Updates

Last Update Posted (Actual)

February 18, 2021

Last Update Submitted That Met QC Criteria

February 17, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IKDC-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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