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

Chinese PLA General Hospital (301 Hospital)

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Primary Mediastinal Large B-cell Lymphoma

Treatments: Drug: GVD chemotherapy; Drug: Decitabine; Drug: SHR-1210

Study type: Interventional

Funder types: Other

Identifiers

NCT03346642

CHN-PLAGH-BT-025

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

GVD and SHR-1210 with or without Decitabine

Experimental group

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.

Treatment:

Drug: SHR-1210

Drug: GVD chemotherapy

Drug: Decitabine