Genotype-guided Treatment in DLBCL

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 rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-X) versus rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma

Official Title
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A Study Comparing the Efficacy and Safety of Genotype-guided R-CHOP-X Versus R-CHOP in Patients With Diffuse Large B-Cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone
* Drug: Orelabrutinib
* Drug: Lenalidomide
* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement) Availability of archival or freshly collected tumor tissue before study enrolment International Prognostic Index (IPI) score of 2-5 or 1 with bulky disease Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 Life expectancy greater than or equal to (>/=) 6 months The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research Exclusion Criteria: Previous chemotherapy. Previous stem cell transplantation. 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 Patients with central nervous system (CNS) lymphoma Primary mediastinal large B-cell lymphoma Left ventricular ejection fraction<50% Laboratory measures meet the following criteria at screening (unless caused by lymphoma): Neutrophils<1.5×10^9/L Platelets<75×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement) ALT or AST is 2 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 Positive test results for chronic hepatitis B and hepatitis C 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 Require treatment with strong/moderate CYP3A inhibitors or inducers. Inability to swallow capsules or presence of diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, post-bariatric surgery, inflammatory bowel disease and complete or incomplete intestinal obstruction Other medical conditions determined by the researchers that may affect the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: R-CHOP-X<br>Patients in R-CHOP-X group will receive rituximab 375 mg/m² IV on day 1, cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 2, and prednisone 100 mg/day PO on days 2-6 of every 21-day cycle for the first cycle. For the remaining 5 cycles, they will receive orelabrutinib 150 mg/day PO on days 1-21, or lenalidomide 25 mg/day PO on days 2-11, or decitabine 10 mg/m² IV on days -5 to -1 followed by standard R-CHOP of every 21-day cycle. | Drug: Rituximab<br>* Rituximab IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Doxorubicin<br>* Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Vincristine<br>* Vincristine IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Prednisone<br>* Prednisone PO will be administered as per the schedule specified in the respective arm.<br>Drug: Orelabrutinib<br>* Orelabrutinib PO will be administered as per the schedule specified in the respective arm.<br>Drug: Lenalidomide<br>* Lenalidomide PO will be administered as per the schedule specified in the respective arm.<br>Drug: Decitabine<br>* Decitabine IV infusion will be administered as per the schedule specified in the respective arm.<br>|
| Active Comparator: R-CHOP<br>Patients in R-CHOP group will receive rituximab 375 mg/m² IV on day 1, cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² iv, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 2, and prednisone 100 mg/day PO on days 2-6 of every 21-day cycle for 6 cycles. | Drug: Rituximab<br>* Rituximab IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Doxorubicin<br>* Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Vincristine<br>* Vincristine IV infusion will be administered as per the schedule specified in the respective arm.<br>Drug: Prednisone<br>* Prednisone PO will be administered as per the schedule specified in the respective arm.<br>|

What is the study measuring?
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Primary 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) | 

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 [Cycle length=21 days] | 
| 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 |