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

NCT03346642 | Unknown Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Primary Mediastinal Large B-cell Lymphoma

Keywords

Relapsed/Refractory; primary mediastinal large B-cell lymphoma; PD-1 antibody; Decitabine; GVD chemotherapy

Outcome Measures

Primary Outcomes (2)

• Number of Subjects with treatment-related adverse events (AEs)

  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)

  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 Outcomes (3)

• Complete response (CR) rate

  Up to 2 years after completion of study treatment

• Median progression-free survival (PFS) time

  Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.

• Median overall survival (OS) time

  Patients will be followed until death, withdrawal from study, or until 2 years.

Study Arms (1)

GVD and SHR-1210 with or without Decitabine

EXPERIMENTAL

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; Drug: GVD chemotherapy; Drug: SHR-1210

Interventions

Decitabine DRUG

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.

GVD and SHR-1210 with or without Decitabine

GVD chemotherapy DRUG

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.

GVD and SHR-1210 with or without Decitabine

SHR-1210 DRUG

SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Also known as: PD-1 antibody, PD-1 inhibitor

GVD and SHR-1210 with or without Decitabine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.

You may not qualify if:

• 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.
• ） Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (2)

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

Decitabine; camrelizumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2017
• First Posted: November 17, 2017
• Study Start: May 1, 2017
• Primary Completion: March 1, 2019
• Study Completion: October 1, 2019
• Last Updated: December 3, 2018

Record last verified: 2018-11

Locations

CN (2)