Genotype-guided Treatment in DLBCL

Sponsor

Ruijin Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05351346

Collaborator

(none)

1,100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Orelabrutinib Drug: Lenalidomide Drug: Decitabine	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP-X Patients in R-CHOP-X group will receive rituximab 375 mg/m² IV, 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 orelabrutinib 150 mg/day PO on days 1-21, or lenalidomide 25 mg/day PO on days 1-10, or decitabine 10 mg/m² IV on days -5 to -1 followed by standard R-CHOP of every 21-day cycle.	Drug: Rituximab Rituximab IV infusion will be administered as per the schedule specified in the respective arm. Drug: Cyclophosphamide Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm. Drug: Doxorubicin Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm. Drug: Vincristine Vincristine IV infusion will be administered as per the schedule specified in the respective arm. Drug: Prednisone Prednisone PO will be administered as per the schedule specified in the respective arm. Drug: Orelabrutinib Orelabrutinib PO will be administered as per the schedule specified in the respective arm. Drug: Lenalidomide Lenalidomide PO will be administered as per the schedule specified in the respective arm. Drug: Decitabine Decitabine IV infusion will be administered as per the schedule specified in the respective arm.
Active Comparator: R-CHOP 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 Rituximab IV infusion will be administered as per the schedule specified in the respective arm. Drug: Cyclophosphamide Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm. Drug: Doxorubicin Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm. Drug: Vincristine Vincristine IV infusion will be administered as per the schedule specified in the respective arm. Drug: Prednisone Prednisone PO will be administered as per the schedule specified in the respective arm.

Arm

Intervention/Treatment

Experimental: R-CHOP-X

Patients in R-CHOP-X group will receive rituximab 375 mg/m² IV, 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 orelabrutinib 150 mg/day PO on days 1-21, or lenalidomide 25 mg/day PO on days 1-10, or decitabine 10 mg/m² IV on days -5 to -1 followed by standard R-CHOP of every 21-day cycle.

Drug: Rituximab

Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Cyclophosphamide

Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Doxorubicin

Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Vincristine

Vincristine IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Prednisone

Prednisone PO will be administered as per the schedule specified in the respective arm.

Drug: Orelabrutinib

Orelabrutinib PO will be administered as per the schedule specified in the respective arm.

Drug: Lenalidomide

Lenalidomide PO will be administered as per the schedule specified in the respective arm.

Drug: Decitabine

Decitabine IV infusion will be administered as per the schedule specified in the respective arm.

Active Comparator: R-CHOP

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

Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Cyclophosphamide

Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Doxorubicin

Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Vincristine

Vincristine IV infusion will be administered as per the schedule specified in the respective arm.

Drug: Prednisone

Prednisone PO will be administered as per the schedule specified in the respective arm.

Outcome Measures

Primary Outcome Measures

Progression-free survival [Baseline up to data cut-off (up to approximately 2 years)]
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.

Secondary Outcome Measures

Complete response rate [End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Overall survival [Baseline up to data cut-off (up to approximately 2 years)]
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [From enrollment to study completion, a maximum of 4 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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