Targeted Drug Combined With CHOP in the Treatment of Newly Diagnosed Peripheral T-cell Lymphoma

The Efficacy and Safety of Targeted Drug in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in the Treatment of Newly Diagnosed Peripheral T-Cell Lymphoma

This prospective，multi-center，open-label, controlled study will evaluate the efficacy and safety of targeted drug in combination with CHOP in treatment of newly diagnosed peripheral T-cell lymphoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: CHOP; Drug: CHOP+X

Detailed Description

Peripheral T-cell lymphoma (PTCL）is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for ~10%. Patients with PTCL still have poor treatment response and prognosis under conventional CHOP regimen. There is no standard of care for those patients. Targeted drugs are warranted in this group of patients to improve survival. This prospective，multi-center，open-label, controlled study will evaluate the efficacy and safety of targeted drug in combination with CHOP in treatment of newly diagnosed peripheral T-cell lymphoma.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Department of Hematology, Peking University Third Hospital, Beijing, China
  • Chengdu, China
    • Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  • Fuzhou, China
    • Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Union Hospital, Fujian Institute of Hematology, Fuzhou, China
  • Shandong, China
    • Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
  • Shanghai, China
    • Shanghai Ruijin Hospital
  • Wuhan, China
    • Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Wuhan, China
    • Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed peripheral T-cell lymphoma based on 2016 WHO classification with enough tumor sample for NGS
• Treatment naive
• Age ≥ 18 years
• Must has measurable lesion in CT or PET-CT prior to treatment
• ECOG 0,1,2
• Informed consented

Exclusion Criteria:

• ALCL,ALK positive, NK/T-cell leukemia, adult T-cell lymphoma/leukemia, T-LGL
• 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<50*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 or HCV-RNA positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CHOP; Patients in this arm will receive conventional CHOP regimen for 6 cycles	Drug: CHOP; Cyclophosphamide 750mg/m2, ivgtt D1, doxorubicin 50mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses
Experimental: CHOP+X; Patients in this arm will receive targeted drug in combination with conventional CHOP regimen for 6 cycles, based on NGS results	Drug: CHOP+X; X: X(i.e. targeted drug) will decided by NGS results as following. Decitabine 10mg/m2 ivgtt D-5 to-1 if with TP53 gene muation. Azacitadine 100mg/day ivgtt D-7 to -1 if with TET2/KMT2D gene mutation. Chidamide 20mg/day po D1,4,8,11 if with CREBBP/EP300 gene mutation. Lenalidomide 25mg/day po D1-10 if without gene mutation above. X will be added from the second cycle CHOP:Cyclophosphamide 750mg/m2, ivgtt D1, doxorubicin 50mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses

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)
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)
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)

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): July 29, 2020
• Primary Completion (Actual): April 20, 2023
• Study Completion (Estimated): April 1, 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): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 10, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Targeted therapy; Peripheral T-cell lymphoma
• 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
• Other Study ID Numbers: RJ-PTCL-1

Drug and device information, study documents

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