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

Primary Purpose

Primary Mediastinal Large B-cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Decitabine

GVD chemotherapy

SHR-1210

About this trial

This is an interventional treatment trial for Primary Mediastinal Large B-cell Lymphoma focused on measuring Relapsed/Refractory, primary mediastinal large B-cell lymphoma, PD-1 antibody, Decitabine, GVD chemotherapy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Biotherapeutic Department and Pediatrics Department of Chinese PLA General HospitalRecruiting
Biotherapeutic Department of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GVD and SHR-1210 with or without Decitabine

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Subjects with treatment-related adverse events (AEs)

Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.

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.

Secondary Outcome Measures

Complete response (CR) rate

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

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

OS time was measured from the study entry to the date of death.

Full Information

NCT ID

NCT03346642

First Posted

October 7, 2017

Last Updated

November 29, 2018

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03346642

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Unknown status

Study Start Date

May 1, 2017 (Actual)

Primary Completion Date

March 1, 2019 (Anticipated)

Study Completion Date

October 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Mediastinal Large B-cell Lymphoma

Keywords

Relapsed/Refractory, primary mediastinal large B-cell lymphoma, PD-1 antibody, Decitabine, GVD chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GVD and SHR-1210 with or without Decitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Decitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

GVD chemotherapy

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

SHR-1210

Other Intervention Name(s)

PD-1 antibody, PD-1 inhibitor

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Subjects with treatment-related adverse events (AEs)

Description

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

Title

Objective response rate (ORR)

Description

Time Frame

Enrolled patients will be followed until death, withdrawal from study, or until 2 years.

Secondary Outcome Measure Information:

Title

Complete response (CR) rate

Description

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

Title

Median progression-free survival (PFS) time

Description

Time Frame

Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.

Title

Median overall survival (OS) time

Description

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Weidong Han, Doctor

Phone

86-10-66937463

hanwdrsw@sina.com

First Name & Middle Initial & Last Name & Degree

Qingming Yang, Doctor

Phone

86-10-55499341

yangqm@medmail.com.cn

First Name & Middle Initial & Last Name & Degree

Wenying Zhang

First Name & Middle Initial & Last Name & Degree

Qian Mei

First Name & Middle Initial & Last Name & Degree

Yang Liu

First Name & Middle Initial & Last Name & Degree

Weidong Han

First Name & Middle Initial & Last Name & Degree

Qingming Yang

First Name & Middle Initial & Last Name & Degree

Hejin Jia

First Name & Middle Initial & Last Name & Degree

Jing Nie

First Name & Middle Initial & Last Name & Degree

Chunmeng Wang

First Name & Middle Initial & Last Name & Degree

Yan Zhang

First Name & Middle Initial & Last Name & Degree

Kaichao Feng

First Name & Middle Initial & Last Name & Degree

Meixia Chen

First Name & Middle Initial & Last Name & Degree

Lu Shi

First Name & Middle Initial & Last Name & Degree

Xiang Li

First Name & Middle Initial & Last Name & Degree

Liang Dong

Facility Name

Biotherapeutic Department of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Weidong Han, Doctor

Phone

86-10-66937463

hanwdrsw@sina.com

First Name & Middle Initial & Last Name & Degree

Qingming Yang, Doctor

Phone

86-10-55499341

yangqm@medmail.com.cn

12. IPD Sharing Statement

Learn more about this trial

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

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