Genotype-guided Treatment in DLBCL

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

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

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Lenalidomide; Drug: Orelabrutinib; Drug: Decitabine

• Study Type: Interventional
• Enrollment (Anticipated): 1100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: 610707 +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu; Phone Number: 610707 +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Weili Zhao, M.D. and Ph.D; Phone Number: 13512112076; Email: zhao.weili@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Prednisone; Prednisone PO 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.
Experimental: R-CHOP-X; 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; 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: Prednisone; Prednisone PO 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: Lenalidomide; Lenalidomide 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: Decitabine; Decitabine IV infusion will be administered as per the schedule specified in the respective arm.

What is the study measuring?

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
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
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)
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]

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: April 24, 2022
• First Submitted That Met QC Criteria: April 24, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Decitabine; Lenalidomide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: GUIDANCE-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No