Clinical trial NCT05320640: Study of Chidamide, Decitabine and Immune Checkpoint Inhibitors in R/R NHL and Advanced Solid Tumors
Official title: A PhaseⅠ/Ⅱ Trial of Chidamide，Decitabine and Immune Checkpoint Inhibitors in Relapsed/Refractory Non-Hodgkin Lymphoma and Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Non-Hodgkin Lymphoma
Advanced Solid Tumors
Keywords: Relapsed/Refractory Non-Hodgkin Lymphoma
Advanced Solid Tumors
Chidamide
Decitabine
Immune Checkpoint Inhibitors
Chemotherapy free regimen
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2022-04-11
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 years
measure: Adverse events
timeFrame: 3 years
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: 3 years
measure: Progression-free survival (PFS)
timeFrame: 3 years
Other outcomes:
measure: Biomarkers predictive of response
timeFrame: 3 years
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department, Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Biotherapeutic Department, Chinese PLA General Hospital
name: Weidong Han, Prfessor
role: PRINCIPAL_INVESTIGATOR
References: