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

Sponsor

Chinese PLA General Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03346642

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Mediastinal Large B-cell Lymphoma	Drug: Decitabine Drug: GVD chemotherapy Drug: SHR-1210	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combined Chemotherapy and PD-1 Antibody(SHR-1210) With or Without Low-dose Decitabine Priming for Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL):Two Stage, Phase I/II Trail

Actual Study Start Date :

May 1, 2017

Anticipated Primary Completion Date :

Mar 1, 2019

Anticipated Study Completion Date :

Oct 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GVD and SHR-1210 with or without 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.	Drug: Decitabine 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. Drug: GVD chemotherapy 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. Drug: SHR-1210 SHR-1210 is a humanized anti-PD-1 monoclonal antibody. Other Names: PD-1 antibody, PD-1 inhibitor

Arm

Intervention/Treatment

Experimental: GVD and SHR-1210 with or without 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.

Drug: Decitabine

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.

Drug: GVD chemotherapy

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.

Drug: SHR-1210

SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Other Names:

PD-1 antibody, PD-1 inhibitor

Outcome Measures

Primary Outcome Measures

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

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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital	Beijing	Beijing	China	100853
2	Biotherapeutic Department of Chinese PLA General Hospital	Beijing	Beijing	China	100853