Chidamide in Combination With Decitabine in Non-Hodgkin's Lymphoma Relapsed After Chimeric Antigen Receptor

Chidamide in Combination With Decitabine in Non-Hodgkin's Lymphoma Relapsed After Chimeric Antigen Receptor : An Open-label Phase I/II Trial

This is a Phase I/II clinical trial for patients with r/r Non-Hodgkin's Lymphoma relapsed after chimeric antigen receptor T cells infusion. The purpose is to evaluate the safety and efficacy of the treatment with chidamide in combination with decitabine.

Study Overview

• Status: Recruiting
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: Chidamide; Drug: Decitabine; Drug: Camrelizumab

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital
      • Contact: Weidong D Han, Doctor; Phone Number: +86-10-66937463; Email: hanwdrsw@sina.com
      • Contact: C, Doctor
      • Sub-Investigator: Yajing Zhang
      • Sub-Investigator: Chunmeng Wang
      • Sub-Investigator: Zhiqiang Wu
      • Sub-Investigator: Yao Wang
      • Sub-Investigator: Chuan Tong
      • Sub-Investigator: Hanren Dai
      • Sub-Investigator: Jing Nie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have histological confirmation of Non-Hodgkin lymphoma (NHL) and relapsed after chimeric antigen receptor T cells infusion.
2. 18 to 65 years of age.
3. ECOG performance of less than 2.
4. Life expectancy of at least 3 months.
5. Subjects with lymphoma must have at least one measureable new lesion >1.5cm as defined by lymphoma response criteria.
6. Subjects must have relapsed after chimeric antigen receptor T cells infusion without any intervention treatment prior to Day 1.
7. Subjects must have adequate marrow, live, renal and heart functions.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in one month .
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
7. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chidamide in combination with decitabine; chidamide 10mg/day, days 1-5, 20mg/day, day 8, 11,15, 18; decitabine 10 mg/day, days 1-5, every 3 weeks	Drug: Chidamide; Chidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can Induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance; Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.; Drug: Decitabine; Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
Experimental: decitabine in combination with Camrelizumab; decitabine 10 mg/day, days 1-5, every 3 weeks; camrelizumab 200mg d6	Drug: Decitabine; Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.; Drug: Camrelizumab; Camrelizumab is a humanized anti-PD-1 monoclonal antibody.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	CR rate assess by investigators per the 2014 Lugano classification rate of subjects achieved complete response in all evaluable subjects	2 years
Adverse events	Adverse events were defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0)	2 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 4, 2020
• Primary Completion (Anticipated): April 4, 2024
• Study Completion (Anticipated): April 4, 2026

Study Registration Dates

• First Submitted: April 4, 2020
• First Submitted That Met QC Criteria: April 4, 2020
• First Posted (Actual): April 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2020
• Last Update Submitted That Met QC Criteria: April 4, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: CHN-PLAGH-BT-046

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No