Guidance-04：T-cell Lymphoma Series：A Genotype-guided Therapy in Newly Diagnosed Patients With Peripheral T-cell Lymphoma （THEORY Study）
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 75
Healthy Volunteers: f
View:
• 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
Locations
Other Locations
China
Ruijin hospital
RECRUITING
Shanghai
Contact Information
Primary
Weili Zhao
zwl_trial@163.com
+862164370045
Backup
Pengpeng Xu
pengpeng_xu@126.com
+862164370045
Time Frame
Start Date: 2023-02-13
Estimated Completion Date: 2028-07-15
Participants
Target number of participants: 264
Treatments
Experimental: T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP
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.
Experimental: T2: CHOP+duvelisib+5-Azacitidine vs CHOP
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.
Experimental: T3: CHOP+chidamide+tislelizumab （CHOPX2）vs CHOP
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.
Related Therapeutic Areas
Sponsors
Leads: Ruijin Hospital
Collaborators: The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Xiamen University, West China Hospital, The Second Affiliated Hospital of Harbin Medical University, Peking University People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanfang Hospital, Southern Medical University, Sun Yat-sen University, Peking University Third Hospital, The First Affiliated Hospital of Soochow University, Beijing Tongren Hospital, The First Affiliated Hospital of Anhui Medical University, The First Hospital of Jilin University, Wuhan TongJi Hospital, Anhui Provincial Cancer Hospital