A Study of Anti-PD-1 Combinations of D-CIK Immunotherapy and Axitinib in Advanced Ranal Carcinoma

November 8, 2018 updated by: ZHOU FANGJIAN, Sun Yat-sen University

A Study of Anti-PD-1( Pembrolizumab) Combinations of D-CIK (Cytokine-induced Killer Cells Are Stimulated Using Mature Dendritic Cells) Immunotherapy and Axitinib in Advanced Ranal Carcinoma

Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and low dose anti-PD-1 antibody in patients with metastatic renal cell carcinoma treated with axitinib.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a phase II, single arm study to investigate the safety and efficacy of pembrolizumab-activated autologous D-CIK cells (CIK:Cytokine-induced killer, D-CIK:CIK cells are stimulated using mature dendritic cells) with Axitinib in patients with advanced kidney cancer.

Heparinized peripheral blood was obtained from participants over a 1-week period. PBMCs(Peripheral blood mononuclear cells) were separated by Ficoll-Hypaque gradient centrifugation, suspended in X-VIVO 15 serum-free medium, and culture with 1000 U/ml rhIFN-γfor the first 24 h, followed by stimulation with 100 ng/ml OKT-3 , 1000 U/ml rhIL-2 and 100 U/ml IL-1α to activate the CIK.Dendritic cells were incubated with CIK. Fresh medium containing 1000 U/ml rhIL-2 was added every 2 days and the cell density was maintained at 2×10^6 cells/mL.D-CIK were harvested, washed, and resuspended after culture for 14 days. Before cell transfer,D-CIK were incubated with anti-PD-1 antibody(Pembrolizumab (Merck & Co., Inc.) is a humanized IgG4 anti-PD-1 monoclonal antibody that binds to PD-1 to prevent it from engaging with PD-L1 or PD-L2.), and a fraction of the D-CIK were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous D-CIK (1.0-1.5*10^10 cells) were transferred to patients via intravenous infusion.

The present study was designed with Simon's best two stage study to explore the efficacy and safety of low-dose pembrolizumab in the treatment of patients with advanced renal cancer by D-CIK re-transfusion combined with Axitinib in vitro. The expected effective rate of the combined treatment is set at 60%, and if the effective rate is less than 30%, the effective rate of the combined treatment is considered to be at an undesirable level. The best two-stage design is 3/8, 10/24. In the first stage, 8 patients need to be treated. If the number of effective cases is less than 3, the combined treatment is deemed ineffective and the trial needs to be terminated. If the number of effective cases is more than 3, the phase II trial will be continued, and a total of 24 subjects need to be included.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 2

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

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Cancer Center, Sun Yat-sen University
        • Contact:
        • Principal Investigator:
          • Jian-Chuan Xia, Ph.D
        • Sub-Investigator:
          • Zhi-Ling Zhang, M.D Ph.D

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • advanced renal clear cell carcinoma confirmed by pathology: high-volume disease without systemic treatment(including primary lesion unable to surgery, multiple lymph node metastases or distant metastases), or achieved disease progression after treatment by the anti-angiogenesis therapy (TKI or mTOR inhibitors) or by cytokines or combination therapy
  • Predicted survival >=3 months
  • At least 1 measurable lesion

High-volume disease（meet one of the following criteria）:1. More than 3 sites of lesions with or without primary lesions, and at least 1 lesion routine CT or spiral CT scan >=3cm; 2. Unresected primary lesions (> 10cm), accompanied by 2 metastatic lesions; 3. After nephrectomy, single metastasis, at least 3 metastases, and at least one lesion > 2cm; 4. After nephrectomy, multiple metastatic(>3 organs) and at least one lesion > 2cm.

Exclusion Criteria:

  • Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib
  • Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components
  • Severe cardiovascular and cerebrovascular diseases, uncontrollable severe hypertension and diabetes, severe renal insufficiency or uremia
  • Long-term use of immunosuppressive agents after organ transplantation
  • Immunosuppressive drugs are currently in use
  • People with a clear and serious infection
  • Predicted survival<3 months
  • Patients with T cell lymphoma, myeloma
  • Patients with autoimmune diseases
  • HIV positive, or other immunodeficiency diseases
  • Pregnant or nursing

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: Combinations treatment
Drug: Axitinib 5mg orally twice a day Combination Treatment：Anti-PD-1 Combinations of D-CIK Immunotherapy
Biological: Combinations treatment
Autologous dendritic and cytokine-induced killer cells (D-CIK)(1.0-1.5*10^10 cells)were incubated with low dose anti-PD-1 antibody（pembrolizumab, Merck & Co., Inc.） and were transferred to participants via intravenous infusion .
Other Names:
  • pembrolizumab(Merck & Co., Inc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate（ORR）by irRC and RECIST 1.1
Time Frame: 3 years
The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib,will be assessed using irRC and RECIST 1.1 to determine tumor response.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival（PFS）by irRC and RECIST 1.1
Time Frame: 3 years
The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.
3 years
Overall Survival (OS) by irRC and RECIST 1.1
Time Frame: 3 years
The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival time.
3 years
Duration of Response (DOR) by irRC and RECIST 1.1
Time Frame: 3 years
The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine duration of response.
3 years
The quality of life by EQ-5D-5L and NCCN-FACT FKSI-19 v2.0.
Time Frame: 3 years
The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using EQ-5D-5L and NCCN-FACT FKSI-19 v2.0.to determine the quality of life.
3 years
Severity of adverse events as assessed by CTCAE v4.0
Time Frame: 3 years
3 years

Collaborators and Investigators

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

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Fangjian Zhou, MD.PhD, Director of Urology,Sun Yat-sen University

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)

September 8, 2018

Primary Completion (Anticipated)

October 8, 2020

Study Completion (Anticipated)

November 8, 2021

Study Registration Dates

First Submitted

November 1, 2018

First Submitted That Met QC Criteria

November 8, 2018

First Posted (Actual)

November 9, 2018

Study Record Updates

Last Update Posted (Actual)

November 9, 2018

Last Update Submitted That Met QC Criteria

November 8, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-FXY-023-Urology

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

We did not decide whether to share the subject's personal information

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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