Genotype-guided Treatment in DLBCL
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 |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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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
Inclusion Criteria:
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Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
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Availability of archival or freshly collected tumor tissue before study enrolment
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International Prognostic Index (IPI) score of 2-5 or 1 with bulky disease
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
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Life expectancy greater than or equal to (>/=) 6 months
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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:
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Previous chemotherapy.
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Previous stem cell transplantation.
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History of malignancies except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
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Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
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Patients with central nervous system (CNS) lymphoma
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Primary mediastinal large B-cell lymphoma
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Left ventricular ejection fraction<50%
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Laboratory measures meet the following criteria at screening (unless caused by lymphoma):
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Neutrophils<1.5×10^9/L
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Platelets<75×109/L (Platelets<50×109/L in case of bone marrow involvement)
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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.
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Creatinine is 1.5 times higher than the ULN.
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HIV-infected patients
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Positive test results for chronic hepatitis B and hepatitis C infection
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Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
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Pregnant or lactation
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Require treatment with strong/moderate CYP3A inhibitors or inducers.
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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
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Other medical conditions determined by the researchers that may affect the study
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Ruijin Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GUIDANCE-02