Genotype-guided Treatment in DLBCL

Diffuse Large B Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05351346
• Other study ID #: GUIDANCE-02
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2022
• Est. completion date: June 1, 2026

Study information

• Verified date: March 2023
• Source: Ruijin Hospital
• Contact: Weili Zhao
• Phone: +862164370045
• Email: zwl_trial[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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):

1. Neutrophils<1.5×10^9/L

2. Platelets<75×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement)

3. 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.

4. 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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
• Cyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
• Doxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
• Vincristine
Vincristine IV infusion will be administered as per the schedule specified in the respective arm.
• Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
• Orelabrutinib
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
• Lenalidomide
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
• Decitabine
Decitabine IV infusion will be administered as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (54)

Lead Sponsor

Collaborator

Ruijin Hospital

Affiliated Cancer Hospital of Harbin Medical University, Affiliated Hospital of Guilin Medical College, Affiliated Hospital of Nantong University, Air Force Medical Center. PLA, Beijing Hospital, Beijing Tongren Hospital, Cancer Hospital Affiliated to Xinjiang Medical University, Central South University, China-Japan Friendship Hospital, Fifth Affiliated Hospital of Guangzhou Medical University, First Affiliated Hospital of Chongqing Medical University, First Affiliated Hospital of Harbin Medical University, First Affiliated Hospital Xi'an Jiaotong University, Fudan University, Fujian Medical University Union Hospital, Gansu Cancer Hospital, Harbin Institute of Hematology, Henan Cancer Hospital, Hunan Cancer Hospital, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Pekcing Union Medical College, LanZhou University, Liaoning Cancer Hospital & Institute, Peking University Third Hospital, Qilu Hospital of Shandong University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Ruian People's Hospital, Second Affiliated Hospital of Xi'an Jiaotong University, Shandong Cancer Hospital and Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanxi Province Cancer Hospital, The Affiliated Hospital of Xuzhou Medical University, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The Affiliated Zhongshan Hospital of Dalian University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Anhui Medical University North District, The First Affiliated Hospital of Guangzhou Medical University, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital of University of Science and Technology of China, The First Affiliated Hospital of Xiamen University, The First Affiliated Hospital of Zhengzhou University, The First Hospital of Jilin University, The Second Affiliated Hospital of Dalian Medical University, The Second Hospital of Anhui Medical University, Tongji Hospital, West China Hospital, Sichuan, Wuhan Union Hospital, China, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Yantai Yuhuangding Hospital, Yunnan Cancer Hospital, Yunnan First People's Hospital, Zhongda Hospital, Zhujiang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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)
Secondary	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