Two Stage Study of Combination of Chemotherapy, SHR-1210 and/or Decitabine for Relapsed/Refractory PMBCLs

Phase 1

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

All patients had histologically proven PMBCL, and Radiographically measureable disease.
Eastern Cooperative Oncology Group performance status 0-2
Disease recurring within 6 months after first-line chemotherapy or disease progression while receiving or persistent disease after first-line chemotherapy
Bulky disease was defined as the presence of a mediastinal mass > 4.5 cm in axial diameter or extranodal lesion > 3 cm.
Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
Adequate organ function.
Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria

Known clinically active central nervous system involvement.
Any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
Serious uncontrolled medical disorders or active infections, pulmonary infection especially
Prior organ allograft.
Receiving any other form of immunosuppressive medication, except steroid.
Allogeneic hematopoietic stem cell transplantation within the last 5 years. 6） Known human immunodeficiency virus (HIV). 7） Has received a live vaccine within 30 days prior to first dose of study drug.

8） Women who are pregnant or breastfeeding.

Arm && Interventions

Group	Intervention	Description
GVD and SHR-1210 with or without Decitabine	GVD chemotherapy	This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.
GVD and SHR-1210 with or without Decitabine	SHR-1210	This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.
GVD and SHR-1210 with or without Decitabine	Decitabine	This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.

Primary Outcome Measures

Name	Time	Method
Number of Subjects with treatment-related adverse events (AEs)	Up to 120 days after last administration of SHR-1210	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Objective response rate (ORR)	Enrolled patients will be followed until death, withdrawal from study, or until 2 years.	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.

Secondary Outcome Measures

Name	Time	Method
Median progression-free survival (PFS) time	Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.	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.
Complete response (CR) rate	Up to 2 years after completion of study treatment	The CR rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Median overall survival (OS) time	Patients will be followed until death, withdrawal from study, or until 2 years.	OS time was measured from the study entry to the date of death.

Locations (2): Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
🇨🇳
Beijing, Beijing, China
Biotherapeutic Department of Chinese PLA General Hospital
🇨🇳
Beijing, Beijing, China