Genotype-guided Treatment in DLBCL

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 3

Conditions: Diffuse Large B Cell Lymphoma

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05351346

GUIDANCE-02

Details and patient eligibility

About

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

Enrollment: 1,100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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):

  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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,100 participants in 2 patient groups

R-CHOP-X

Experimental group

Description:

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.

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Lenalidomide

Drug: Rituximab

Drug: Doxorubicin

Drug: Decitabine

Drug: Orelabrutinib

Drug: Cyclophosphamide

R-CHOP

Active Comparator group

Description:

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.

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Rituximab

Drug: Doxorubicin

Drug: Cyclophosphamide