Azacitidine Combined With Chidamide in the Treatment of Newly Diagnosed PTCL Unfit for Conventional Chemotherapy

The Efficacy and Safety of Azacitidine in Combination With Chidamide in the Treatment of Newly Diagnosed Peripheral T-Cell Lymphoma Unfit for Conventional Chemotherapy

This prospective, open-label, single-arm study will evaluate the efficacy and safety of azacitidine in combination with chidamide in treatment of newly diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Azacitidine; Drug: Chidamide

Detailed Description

Peripheral T-cell lymphoma (PTCL is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for ~10%. CHOP regimen has been widely used in PTCL patients even with unfavourable prognosis, with 5-year overall survival rate of 38.5%. Elderly patients seldom benefit from conventional CHOP regimen. A study showed that CR rate was only 18.1% in elderly patients (median age of 80 years old, ranging from 56 to 93 years old).

Azacitidine combined with romidepsin has been proved efficient in relasped or refractory PTCL, with CR rate of 55%. This prospective, open-label, single-arm study will evaluate the efficacy and safety of azacitidine in combination with Chidamide in treatment of newly diagnosed peripheral T-cell lymphoma unfit for conventional chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, PhD，MD; Phone Number: +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu, PhD，MD; Phone Number: +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Ruijin Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed peripheral T-cell lymphoma based on 2016 WHO classification
• Treatment naive
• Age ≥ 18 years
• Unfit for converntional chemotherapy meeting criteria as following but not limited to: age ≥75, ECOG >2，ADL<100 or CCI>1.
• Must has measurable lesion in CT or PET-CT prior to treatment
• Expected lifetime ≥ 3 months
• Informed consented

Exclusion Criteria:

• Has accepted localized or systemic anti-lymphoma treatment
• Has accepted autologous Stem cell transplantation before
• History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix prior to study treatment
• Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease
• Primary CNS lymphoma
• Left EF≤ 50%
• Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/ L ;Platelet<75*10^9/L; ALT or AST >2*ULN; Creatinine>1.5*ULN
• Other uncontrollable medical condition that may that may interfere the participation of the study
• Not able to comply to the protocol for mental or other unknown reasons
• Patients with mentally disorders or other reasons unable to fully comply with the study protocol
• Pregnant or lactation
• HIV infection
• HBV-DNA and HCV-RNA undectable.

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: Aza+Chida; Azacitidine ivgtt D1-7 Chindamide 30mg,PO,twice a week Every 21 days for total 6 courses	Drug: Azacitidine; 100mg D1-7; Drug: Chidamide; 30mg BIW PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria	At the end of Cycle 6 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT.	Baseline up to data cut-off (up to approximately 4 years)
Treatment related mortality	Percentage of death related with treatment on the basis of investigator assessments	Baseline up to data cut-off (up to approximately 4 years)
Overall response rate	Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria	At the end of Cycle 6 (each cycle is 21 days)
Progression free survival	Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
Overall survival	Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 4 years)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events	Baseline up to data cut-off (up to approximately 4 years)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores	The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.	: Baseline (pre-dose [Hour 0] on Cycle1 Day1), Cycle3 Day 1, end of treatment (up to Month 6), every 3 months 1st year, every 6 months 2nd year, and 12 months thereafter up to data cut-off, up to approximately 4 years (cycle length = 21 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating free Deoxyribonucleic Acid (cfDNA) monitoring	CfDNA in peripheral blood assessed by local lab	Baseline up to data cut-off (up to approximately 4 years)
Exploratory biomarker analysis	Exploratory biomarker to predict treatment response and survival	Baseline up to data cut-off (up to approximately 4 years)

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2020
• Primary Completion (Anticipated): June 20, 2022
• Study Completion (Anticipated): June 20, 2024

Study Registration Dates

• First Submitted: July 19, 2020
• First Submitted That Met QC Criteria: July 19, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Targeted therapy; Peripheral T-cell lymphoma; Chemo-free therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: RJ-PTCL-2

Drug and device information, study documents

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