Study of Chidamide, Decitabine and Immune Checkpoint Inhibitors in R/R NHL and Advanced Solid Tumors

A PhaseⅠ/Ⅱ Trial of Chidamide，Decitabine and Immune Checkpoint Inhibitors in Relapsed/Refractory Non-Hodgkin Lymphoma and Advanced Solid Tumors

This phase I/II trial aims to evaluate safety and efficacy of Chidamide, Decitabine and Immune checkpoint inhibitors in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; Relapsed/Refractory Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Chidamide; Drug: Decitabine; Drug: Immune checkpoint inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）

Detailed Description

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. Low-dose decitabine inhibits the activity of DNA methyltransferase, which can increase the expression of tumor antigens and HLA molecules, enhance antigen processing, promote T cell infiltration, and boost effector T cell function. Immune checkpoint inhibitors (ICIs) have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells. In conclusion, we speculate that the chemotherapy free regimen of Chidamide, Decitabine and Immune checkpoint inhibitors may explore a new avenue for therapeutic intervention in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.

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

Contacts and Locations

• Study Contact: Name: Weidong Han, Professor; Phone Number: +86-10-55499341; Email: hanwdrsw@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department, Chinese PLA General Hospital
      • Contact: Han wei dong, Ph.D; Phone Number: +86-10-55499341; Email: hanwdrsw@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 16 to 80 years of age.
2. ECOG performance of less than 3.
3. Life expectancy of at least 3 months.
4. Histopathological confirmed Non-Hodgkin Lymphoma and solid tumors.
5. Patients are relapsed/refractory Non-Hodgkin Lymphoma with ineligible for autologous hematopoietic stem cell transplantation.
6. The guidelines（ASCO/CSCO）recommend patients to participate in clinical trials.
7. Subjects must have at least one measureable target lesion.
8. Willingness to provide written informed consent for the study.

Exclusion Criteria:

1. Active, known or suspected autoimmune diseases.
2. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
3. History of severe hypersensitive reactions to other monoclonal antibodies.
4. History of allergy or intolerance to study drug components.
5. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
6. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
7. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
8. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
9. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
10. Vaccination within 30 days of study enrollment.
11. Active bleeding or known hemorrhagic tendency.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental arm; Drug: Chidamide10mg/day, day1-4; 20mg/day, day8, 11, 15, 18. Drug: Decitabine10mg/day, day1-5. Drug: Immune Checkpoint Inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）. Physicians will decide which ICIs will be used during treatment. 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.; Drug: Decitabine; Low-dose decitabine inhibits the activity of DNA methyltransferase, which can increase tumor antigens and HLA expression, enhance antigen processing, promote T cell infiltration, and boost effector T cell function.; Drug: Immune checkpoint inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）; Immune checkpoint inhibitors (ICIs) have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The percentage of patients with CR or PR was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	3 years
Adverse events	Incidence, nature, and severity of adverse events are graded according to the National Cancer Institute Common Terminology Criteria for adverse events (version5.0).	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Time from the first recording of CR or PR evidence to disease progression or death from any cause was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	3 years
Progression-free survival (PFS)	Time from the date of first administration of the study drug to disease progression or death from any cause.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers predictive of response	Biomarkers from tumor cells, lymphocytes and tumor microenvironment will be assessed for their potential in predicting clinical response.	3 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Weidong Han, Prfessor, Biotherapeutic Department, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: April 2, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Immune Checkpoint Inhibitors; Decitabine; Advanced Solid Tumors; Chidamide; Relapsed/Refractory Non-Hodgkin Lymphoma; Chemotherapy free regimen
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Decitabine; Antibodies; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CHN-PLAGH-BT-069

Drug and device information, study documents

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