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