Genotype-guided Treatment in PTCL

Study Overview
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Brief Summary
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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.

Official Title
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T-cell Lymphoma Series：A Genotype-guided Therapy in Newly Diagnosed Patients With Peripheral T-cell Lymphoma （THEORY Study）

Conditions
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Peripheral T Cell Lymphoma

Intervention / Treatment
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* Drug: CHOP+selinexor+5-Azacitidine
* Drug: CHOP+duvelisib+5-Azacitidine
* Drug: CHOP+chidamide+tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed Peripheral T-cell lymphoma Availability of archival or freshly collected tumor tissue before study enrollment 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHOP+selinexor+5-Azacitidine<br>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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg in phase I triaI on days d1,d8 while selinexor RP2D po in phase II trial followed by standard CHOP of every 21-day cycle. | Drug: CHOP+selinexor+5-Azacitidine<br>* 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg in phase I triaI on days d1,d8 while selinexor RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.<br>|
| Experimental: CHOP+duvelisib+5-Azacitidine<br>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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle. | Drug: CHOP+duvelisib+5-Azacitidine<br>* 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.<br>|
| Experimental: CHOP+chidamide+tislelizumab<br>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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle. | Drug: CHOP+chidamide+tislelizumab<br>* 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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.<br>|

What is the study measuring?
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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. | End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival was defined as the time from the date of randomization 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 2 years) | 
| Overall survival | Overall survival was defined as the time from the date of randomization to the date of death from any cause. | Baseline up to data cut-off (up to approximately 2 years) | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 | 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. | From enrollment to study completion, a maximum of 4 years |