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Trial Title: Genotype-guided Treatment in Newly Diagnosed PTCL

NCT ID: NCT05675813

Condition: Peripheral T Cell Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Azacitidine
Tislelizumab

Conditions: Keywords:
Biomarker-driven
Genetic subtypes
Complete response rate
Phase 1/2
Precision medicine

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: CHOP+selinexor+5-Azacitidine
Description: Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T1 genetic subtype, for the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg qw (d-7, 1, 8) by traditional "3+3" dose escalation methods and decide RP2D of selinexor. Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T1 genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 21-day cycle.
Arm group label: T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP

Intervention type: Drug
Intervention name: CHOP+duvelisib+5-Azacitidine
Description: Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T2 genetic subtype, for the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg bid (d1-14) by traditional "3+3" dose escalation methods and decide RP2D of duvelisib. Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T1 genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 21-day cycle.
Arm group label: T2: CHOP+duvelisib+5-Azacitidine vs CHOP

Intervention type: Drug
Intervention name: CHOP+chidamide+tislelizumab
Description: Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T3 genetic subtype, for the remaining 5 cycles, they will receive tislelizumab 200mg d0 ivgtt and chidamide 20mg or 30mg biw (d1,4,8,11) by traditional "3+3" dose escalation methods and decide RP2D of chidamide. Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T3 genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 21-day cycle.
Arm group label: T3: CHOP+chidamide+tislelizumab (CHOPX2)vs CHOP

Intervention type: Drug
Intervention name: standard CHOP
Description: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on days 1-5 of every 21-day cycle for the 6 cycles.
Arm group label: T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP
Arm group label: T2: CHOP+duvelisib+5-Azacitidine vs CHOP
Arm group label: T3: CHOP+chidamide+tislelizumab (CHOPX2)vs CHOP

Summary: This study includes Phase I and Phase II stages. Phase I is an open-label trial to confirm RP2D of oral targeted agents in three genetic subtypes. Phase II is a multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of genotype-guided targeted agents plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-X2) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with peripheral T-cell lymphoma.

Detailed description: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. Standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy is still the most widely used front-line treatment of PTCL except Brentuximab-CHP application in anaplastic large cell lymphoma (ALCL). The CR rate ranges from 31%-56% in different studies with different PTCL histology compositions. With the exception for ALCL-anaplastic lymphoma kinase (ALK)-positive, the 5-year overall survival (OS) rate is approximately 30%-40% for most subtypes of PTCL patients in current situation, remaining as the unmet medical needs in this disease. Based on genetic subtypes in PTCL, and our previous study exploring targeted agents plus CHOP based on genetic mutations (Guidance-03 study), we conducted this multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of genotype-guided targeted agents plus CHOP (CHOP-X2) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with PTCL. It includes phase I and phase II stages. Patients will receceived stardard CHOP for the first cycle and then obtain the genetic subtypes from tumor NGS befor Cycle 2. In phase I, recommended phase 2 dose (RP2D) of oral targeted agents will be confirmed by traditional "3+3" dose escalation methods. In phase II, patients will receive standard CHOP for the first cycle and then 1:1 be randomized to CHOPX2 or CHOP regimen in each genetic subtypes.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Histologically-confirmed Peripheral T-cell lymphoma - Availability of archival or freshly collected tumor tissue before study enrollment enough for NGS - Evaluable lesion by PET-CT or CT scan - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 - Life expectancy greater than or equal to (>/=) 3 months - Informed consent Exclusion Criteria: - Patients with ALCL and cutaneous TCL - Patients with central nervous system (CNS) lymphoma - History of malignancies except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix - Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases - Laboratory measures meet the following criteria at screening (unless caused by lymphoma): Neutrophils<1.0×10^9/L Platelets<75×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement) ALT or AST is 2.5 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN. Creatinine is 1.5 times higher than the ULN. - HIV-infected patients - Active hepatitis infection - Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol - Pregnant or lactation - Other medical conditions determined by the researchers that may affect the study For T3 should exclude patiens with active autoimmune disease

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Ruijin hospital

Address:
City: Shanghai
Zip: 200025
Country: China

Status: Recruiting

Contact:
Last name: Mingci Cai, MD

Phone: 86-21-64370045

Phone ext: 665251

Investigator:
Last name: Weili Zhao, MD
Email: Principal Investigator

Investigator:
Last name: Shu Cheng, MD
Email: Sub-Investigator

Investigator:
Last name: Mingci Cai, MD
Email: Sub-Investigator

Investigator:
Last name: Yaohui Huang, MD
Email: Sub-Investigator

Start date: February 13, 2023

Completion date: July 15, 2028

Lead sponsor:
Agency: Ruijin Hospital
Agency class: Other

Collaborator:
Agency: The First Affiliated Hospital of Nanchang University
Agency class: Other

Collaborator:
Agency: Peking University Third Hospital
Agency class: Other

Collaborator:
Agency: Wuhan TongJi Hospital
Agency class: Other

Collaborator:
Agency: West China Hospital
Agency class: Other

Collaborator:
Agency: Nanfang Hospital, Southern Medical University
Agency class: Other

Collaborator:
Agency: Anhui Provincial Cancer Hospital
Agency class: Other

Collaborator:
Agency: The First Affiliated Hospital of Soochow University
Agency class: Other

Collaborator:
Agency: The Second Affiliated Hospital of Harbin Medical University
Agency class: Other

Collaborator:
Agency: The First Affiliated Hospital of Xiamen University
Agency class: Other

Collaborator:
Agency: The First Affiliated Hospital of Zhengzhou University
Agency class: Other

Collaborator:
Agency: Beijing Tongren Hospital
Agency class: Other

Collaborator:
Agency: Peking University People's Hospital
Agency class: Other

Collaborator:
Agency: Sun Yat-sen University
Agency class: Other

Collaborator:
Agency: The First Affiliated Hospital of Anhui Medical University
Agency class: Other

Collaborator:
Agency: The First Hospital of Jilin University
Agency class: Other

Source: Ruijin Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05675813

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