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

November 29, 2018 updated by: Han weidong, Chinese PLA General Hospital

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

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Biotherapeutic Department of Chinese PLA General Hospital
        • Contact:
        • Contact:
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
        • Principal Investigator:
          • Yan Zhang
        • Contact:
        • Contact:
        • Principal Investigator:
          • Wenying Zhang
        • Principal Investigator:
          • Qian Mei
        • Principal Investigator:
          • Yang Liu
        • Principal Investigator:
          • Qingming Yang
        • Principal Investigator:
          • Hejin Jia
        • Principal Investigator:
          • Jing Nie
        • Principal Investigator:
          • Chunmeng Wang
        • Sub-Investigator:
          • Kaichao Feng
        • Sub-Investigator:
          • Lu Shi
        • Sub-Investigator:
          • Xiang Li
        • Sub-Investigator:
          • Liang Dong

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. All patients had histologically proven PMBCL, and Radiographically measureable disease.
  2. Eastern Cooperative Oncology Group performance status 0-2
  3. Disease recurring within 6 months after first-line chemotherapy or disease progression while receiving or persistent disease after first-line chemotherapy
  4. Bulky disease was defined as the presence of a mediastinal mass > 4.5 cm in axial diameter or extranodal lesion > 3 cm.
  5. 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.
  6. Adequate organ function.
  7. 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.
  8. 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:

  1. Known clinically active central nervous system involvement.
  2. Any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
  3. Serious uncontrolled medical disorders or active infections, pulmonary infection especially
  4. Prior organ allograft.
  5. Receiving any other form of immunosuppressive medication, except steroid.
  6. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects with treatment-related adverse events (AEs)
Time Frame: 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.
Up to 120 days after last administration of SHR-1210
Objective response rate (ORR)
Time Frame: 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.
Enrolled patients will be followed until death, withdrawal from study, or until 2 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate
Time Frame: 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.
Up to 2 years after completion of study treatment
Median progression-free survival (PFS) time
Time Frame: 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.
Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.
Median overall survival (OS) time
Time Frame: 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.
Patients will be followed until death, withdrawal from study, or until 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2017

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

October 1, 2019

Study Registration Dates

First Submitted

October 7, 2017

First Submitted That Met QC Criteria

November 14, 2017

First Posted (Actual)

November 17, 2017

Study Record Updates

Last Update Posted (Actual)

December 3, 2018

Last Update Submitted That Met QC Criteria

November 29, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-025

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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