This is a two stage, Phase I/II clinical trial for patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). In the first stage, the participants will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody (SHR-1210) treatment. The safety and efficacy of combined regimen will be evaluated. If deemed safe and efficacious, the investigators will proceed to the second stage of the study. In the second stage, the participants will receive GVD chemotherapy and SHR-1210 treatment with low-dose Decitabine priming. The safety and feasibility of combined regimens will be evaluated in phase I study. The feasibility will be accessed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and histocompatibility leukocyte antigen (HLA) expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
GVD regimen is a chemotherapy regimen consisted by Gemcitabine, Vinorelbine and Doxorubicine. Patients will be administrated with Gemcitabine 0.8 g/m2, Vinorelbine 30mg and Doxorubicin 20mg/m2 intravenously infusion.
SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGBiotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGNumber of Subjects with treatment-related adverse events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Time frame: Up to 120 days after last administration of SHR-1210
Objective response rate (ORR)
The antitumor efficacy of the combination treatments as measured by ORR was determined using the International Working Group 2007 criteria for malignant lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-586). Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment. ORR is defined as the sum of CR and PR.
Time frame: Enrolled patients will be followed until death, withdrawal from study, or until 2 years.
Complete response (CR) rate
The CR rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Time frame: Up to 2 years after completion of study treatment
Median progression-free survival (PFS) time
PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined using the International Working Group 2007 criteria for malignant lymphoma.
Time frame: Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.
Median overall survival (OS) time
OS time was measured from the study entry to the date of death.
Time frame: Patients will be followed until death, withdrawal from study, or until 2 years.
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