Genotype-guided Treatment in DLBCL

NCT05351346 | Recruiting Phase 3 DMC

• 1 other identifier: GUIDANCE-02
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 1

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

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Complete response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Overall survival

  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

  From enrollment to study completion, a maximum of 4 years

Study Arms (2)

R-CHOP-X

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Orelabrutinib; Drug: Lenalidomide; Drug: Decitabine

R-CHOP

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Interventions

Rituximab DRUG

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

R-CHOP; R-CHOP-X

Cyclophosphamide DRUG

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

R-CHOP; R-CHOP-X

Doxorubicin DRUG

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

R-CHOP; R-CHOP-X

Vincristine DRUG

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

R-CHOP; R-CHOP-X

Prednisone DRUG

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

R-CHOP; R-CHOP-X

Orelabrutinib DRUG

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

R-CHOP-X

Lenalidomide DRUG

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

R-CHOP-X

Decitabine DRUG

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

R-CHOP-X

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; orelabrutinib; Lenalidomide; Decitabine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; zwl_trial@163.com

Pengpeng Xu

CONTACT

+862164370045; pengpeng_xu@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: First Deputy Director, Hematology Department

Study Record Dates

• First Submitted: April 24, 2022
• First Posted: April 28, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)