A Umbrella Study in R/R PTCL Guided by Molecular Subtypes

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, prospective, open-label, interventional umbrella study to evaluate the efficacy and safety of targeted therapies guided by molecular subtypes in patients with relasped or refractory peripheral T-cell lymphoma.

Official Title
-----------------
A Umbrella Study in Relapsed/Refractory Peripheral T-cell Lymphoma Guided by Molecular Subtypes

Conditions
-----------------
Peripheral T Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Azacitidine Injection
* Drug: Dasatinib
* Drug: Linperlisib
* Drug: Tucidinostat
* Drug: SHR2554
* Drug: Camrelizumab
* Drug: Apatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically-confirmed Peripheral T-cell lymphoma (without central nervous system involvement) Relapsed or refractory disease after first line treatment 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 T3.2 should exclude patiens with active autoimmune disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T1 subtypes based on next generation sequencing results<br>T1 subtypes based on next generation sequencing results | Drug: Azacitidine Injection<br>* Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes<br>Drug: Dasatinib<br>* Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes<br>|
| Experimental: T2 subtypes based on next generation sequencing results<br>T2 subtypes based on next generation sequencing results | Drug: Azacitidine Injection<br>* Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes<br>Drug: Linperlisib<br>* Azacitidine Injection，SC and Linperlisib PO will be administered in T2 subtypes<br>|
| Experimental: T3.1 subtypes based on next generation sequencing results<br>T3.1 subtypes based on next generation sequencing results | Drug: Tucidinostat<br>* Tucidinostat PO and SHR2554 PO will be administered in T3.1 subtypes<br>Drug: SHR2554<br>* Tucidinostat PO and SHR2554 PO will be administered in T3.1 subtypes<br>|
| Experimental: T3.2 subtypes based on next generation sequencing results<br>T3.2 subtypes based on next generation sequencing results | Drug: Camrelizumab<br>* Camrelizumab and Apatinib will be administered in T3.2 subtypes<br>Drug: Apatinib<br>* Camrelizumab and Apatinib will be administered in T3.2 subtypes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of participants with complete and partial 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）(each cycle is 28 days) | 

Secondary 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）(each cycle is 28 days) | 
| Progression-free survival | Progression-free survival was defined as the time from the date of enrollment 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 enrollment to the date of death from any cause. | Baseline up to data cut-off (up to approximately 2 years) | 
| Duration of response | Duration of response was defined as the time from the date of favorable response until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria | 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 |