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
Overview
- Phase
- Phase 1
- Intervention
- Decitabine
- Conditions
- Primary Mediastinal Large B-cell Lymphoma
- Sponsor
- Chinese PLA General Hospital
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Number of Subjects with treatment-related adverse events (AEs)
- Last Updated
- 7 years ago
Overview
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.
Investigators
Han weidong
Principal Investigator
Chinese PLA General Hospital
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
- •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.
Arms & Interventions
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.
Intervention: Decitabine
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.
Intervention: GVD chemotherapy
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.
Intervention: SHR-1210
Outcomes
Primary Outcomes
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.
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 Outcomes
- Median progression-free survival (PFS) time(Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.)
- Complete response (CR) rate(Up to 2 years after completion of study treatment)
- Median overall survival (OS) time(Patients will be followed until death, withdrawal from study, or until 2 years.)