Clinical trial NCT03346642: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Primary Mediastinal Large B-cell Lymphoma
Keywords: Relapsed/Refractory
primary mediastinal large B-cell lymphoma
PD-1 antibody
Decitabine
GVD chemotherapy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 \> 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.

Primary outcomes:
measure: Number of Subjects with treatment-related adverse events (AEs)
timeFrame: Up to 120 days after last administration of SHR-1210
measure: Objective response rate (ORR)
timeFrame: Enrolled patients will be followed until death, withdrawal from study, or until 2 years.
Secondary outcomes:
measure: Complete response (CR) rate
timeFrame: Up to 2 years after completion of study treatment
measure: Median progression-free survival (PFS) time
timeFrame: Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.
measure: Median overall survival (OS) time
timeFrame: Patients will be followed until death, withdrawal from study, or until 2 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
References: