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

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ClinicalTrials.gov Identifier: NCT03346642
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : November 20, 2017
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Brief Summary:
In this study, participants with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody(SHR-1210) with or without low-dose Decitabine priming. The safety and feasibility of combined regimens will be evaluated in phase I study. The subsequent phase II study will access the efficacy of the combined regimens.

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel 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):An Open Label, Two-arms, Phase I/II Trail
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : June 1, 2018
Estimated Study Completion Date : October 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Decitabine primed GVD and SHR-1210 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 Name: PD-1 antibody, PD-1 inhibitor

Experimental: GVD and SHR-1210 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 Name: PD-1 antibody, PD-1 inhibitor




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 >7.5 cm in axial diameter or extranodal lesion >6 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03346642


Locations
China, Beijing
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Weidong Han, Doctor    86-10-66937463    hanwdrsw@sina.com   
Contact: Qingming Yang, Doctor    86-10-55499341    yangqm@medmail.com.cn   
Principal Investigator: Wenying Zhang         
Principal Investigator: Qian Mei         
Principal Investigator: Yang Liu         
Principal Investigator: Weidong Han         
Principal Investigator: Qingming Yang         
Principal Investigator: Hejin Jia         
Principal Investigator: Jing Nie         
Principal Investigator: Chunmeng Wang         
Principal Investigator: Yan Zhang         
Sub-Investigator: Kaichao Feng         
Sub-Investigator: Meixia Chen         
Sub-Investigator: Lu Shi         
Sub-Investigator: Xiang Li         
Sub-Investigator: Liang Dong         
Biotherapeutic Department of Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Weidong Han, Doctor    86-10-66937463    hanwdrsw@sina.com   
Contact: Qingming Yang, Doctor    86-10-55499341    yangqm@medmail.com.cn   
Sponsors and Collaborators
Chinese PLA General Hospital

Responsible Party: Han weidong, Principal Investigator, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT03346642     History of Changes
Other Study ID Numbers: CHN-PLAGH-BT-025
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: November 20, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Han weidong, Chinese PLA General Hospital:
Relapsed/Refractory
primary mediastinal large B-cell lymphoma
PD-1 antibody
Decitabine
GVD chemotherapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies
Immunoglobulins
Decitabine
Azacitidine
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors