The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Siriraj Hospital
Sponsor:
Collaborator:
Mahidol University
Information provided by (Responsible Party):
Adisak Wongkajornsilp, Siriraj Hospital
ClinicalTrials.gov Identifier:
NCT01868490
First received: May 30, 2013
Last updated: NA
Last verified: May 2013
History: No changes posted
  Purpose

Cytokine-induced killer (CIK) cells exhibit high proliferation rate and cytotoxic activity in vitro. The major effector cells are the CD3+CD56+ subset. The cytolytic activity of CIK cells being independent of MHC restriction implies feasibility in using CIK cells allogeneic to the tumors. Experiments to block the MHC class-I and -II pathways on tumors-RNA transfected DCs showed that only MHC class-I blocking led to a significant reduction of heterogeneous CIK cells cytotoxicity after the co-culture. The safety of CIK cells was demonstrated by the lack of cytotoxicity toward autologous as well as allogeneic normal cells. Co-culture of CIK cells with dendritic cells (DCs) has been reported by us and others in a myriad of cancer (e.g., cholangiocarcinoma, osteosarcoma, glioblastoma multiforme, multiple myeloma, hepatocellular carcinoma, pancreatic carcinoma, renal & colon carcinoma, murine leukemia & lymphoma showing enhancement of anti-tumor cytotoxicity of CIK cell in all. The co-culture of CIK cells with DCs were reported to decrease the number of professional regulatory/ suppressor T cells (Treg, CD4+CD25+ cells) and decrease the secretion of IL-10, an immune suppressor cytokine, whereas the cytotoxic activity against target cells increased.

We have recently brought CIK cells through the preclinical phase (animal study) of human cholangiocarcinoma treatment. Cholangiocarcinoma (CCA), is a bile duct epithelial cancer endemic in the Northeast of Thailand, with an increasing incidence discernible in Europe and North America. Conventional treatments including surgery, chemotherapy, and radiation do not bring satisfactory survival due to anatomic location, presence of metastases, and high recurrent rates. These unsatisfactory outcomes urge to search innovative treatments such as immunotherapy. We reported the safety and efficacy of CIK cells in SCID mice model for cholangiocarcinoma. Several conditions of human CIK cells were examined using ex vivo cytotoxic assay and SCID mice pre-inoculated with human cholangiocarcinoma cells. We monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs). Tumor-infiltrating human CD3+ cells were observed from day 2 - 14, but not in normal tissues elsewhere. These altogether indicated the specific homing of CIK cells to tumor mass. All animals did not exhibit any noticeable adverse reaction from the CIK treatments. The CD3+CD56+ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells produced similar efficacy and more feasible for clinical application.

With a complete array of in vitro and in vivo study, the next rational step is moving forward to phase I/II clinical trials for a number of specified solid tumors (i.e., cholangiocarcinoma, osteosarcoma, and glioblastoma multiforme, nueroblastoma) using the optimized autologous CIK cells. Subjects without prior exposure to or weaned for at least 3 months from chemotherapy can be recruited to maintain the integrity of their immunological system, a critical factor for a successful immunotherapy.


Condition Intervention Phase
Cholangiocarcinoma
Drug: cytokine induced killer cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of The Adoptive Immunotherapy for Solid Tumors Using Modified Autologous Cytokine-induced Killer Cells.

Resource links provided by NLM:


Further study details as provided by Siriraj Hospital:

Primary Outcome Measures:
  • MRI scan for monitoring of tumor size and CIK cell-homing, Fluorescence-activated cell sorting (FACS) analysis [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Survival rate [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 13
Study Start Date: April 2009
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: drug
single-group studies
Drug: cytokine induced killer cells
at least 10*9 CIK cells, IV on day 0, 14, 28

  Eligibility

Ages Eligible for Study:   8 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must be at least 18 year-old, or allowance from their parent if younger than that.
  2. Patient must have histologically or cytologically confirmed advanced Cholangiocarcinoma by oncologist
  3. Cholangiocarcinoma have been failing to current treatment.
  4. Patient is healthy by getting an Eastern Co-operative Oncology Group (ECOG) performances status of 0, 1 or 2.
  5. Any of the following lab data

    a. Hematology:

    • Hb > 8 g/dl
    • Absolute neutrophil count (ANC) > 1,500 cells/mm3
    • Absolute lymphocyte count > 1,000 cells/mm3
    • Platelet > 100x109/L
  6. Patient must have a life expectancy of at least 12 weeks by

    a. Biochemistry:

    • Serum total bilirubin < 3 mg/dl
    • Serum creatinine < 2 mg/dl
  7. Patients will to comply and provide written informed consent prior to enrollment into the study.

Exclusion Criteria:

  1. Patients received chemotherapy within 4 weeks before study entry.
  2. Active uncontrolled infection
  3. Concurrent anti-cancer treatment in another investigational trial, including immunotherapy in last 30 days
  4. Pregnant or lactating woman, or women of child bearing potential or less than one year after menopause (unless surgically sterile) with urine pregnancy test positive
  5. Concurrent steroid therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01868490

Contacts
Contact: Adisak Wongkajornsilp, M.D.Ph.D. +66(0)2-419-8573 ext - siawj@mahidol.ac.th
Contact: Apaporn Suthimanus, M.D. +66(0)2-419-7576 ext - siapq@mahidol.ac.th

Locations
Thailand
Siriraj Clinical Research Center, Siriraj Hospital Recruiting
Bangkoknoi, Bangkok, Thailand, 10700
Contact: Adisak Wongkajornsilp, M.D. Ph.D.    +66(0)2-419-8573 ext -    siawj@mahidol.ac.th   
Contact: Apaporn Suthimanus, M.D.    +66(0)2-419-7576 ext -    siapq@mahidol.ac.th   
Principal Investigator: Adisak Wongkajornsilp, M.D. Ph.D.         
Sponsors and Collaborators
Siriraj Hospital
Mahidol University
  More Information

No publications provided

Responsible Party: Adisak Wongkajornsilp, Pharmacology department, Faculty of medicine, Siriraj Hospital, Siriraj Hospital
ClinicalTrials.gov Identifier: NCT01868490     History of Changes
Obsolete Identifiers: NCT01573455
Other Study ID Numbers: 215-3-2552
Study First Received: May 30, 2013
Last Updated: May 30, 2013
Health Authority: Thailand:Siriraj Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Siriraj Hospital:
Cholangiocarcinoma
Cytokine induced killer cells
CIK
Treg
Th17

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 15, 2014