A Phase II Trial of 4 vs 6 Cycles of CHP Combined With Polatuzumab Vedotin-Rituximab in Untreated DLBCL Patients With IPI 0-1
- Conditions
- DLBCL - Diffuse Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT07034508
- Brief Summary
This is an open-label, multicentre, randomized phase II non-inferiority trial aiming to compare the efficacy and safety of 4 versus 6 cycles of CHP (administered at 21-day intervals), both in combination with 6 cycles of polatuzumab vedotin and rituximab, in previously untreated patients with diffuse large B-cell lymphoma (DLBCL) and an International Prognostic Index (IPI) score of 0-1. The study's primary objective is to determine if shorter CHP duration can achieve comparable outcomes to the standard 6-cycle regimen when combined with polatuzumab vedotin and rituximab
- Detailed Description
The POLARIX study demonstrated that the Pola-R-CHP regimen (replacing vincristine in R-CHOP with Pola) significantly improves progression-free survival (PFS) and is safer than traditional R-CHOP. The FLYER study suggested that 4 cycles of R-CHOP followed by 2 additional doses of rituximab in young, low-risk DLBCL patients (IPI 0-1) are as effective as 6 cycles of R-CHOP and result in lower toxicity. Based on the efficacy of Pola-R-CHP and the potential for reducing treatment intensity in low-risk patients, this study will evaluate whether 4 cycles of Pola-R-CHP followed by 2 cycles of Pola-R are non-inferior to 6 cycles of Pola-R-CHP in treatment-naive low-risk DLBCL patients (IPI 0-1), with a potentially better safety profile.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 134
- Newly diagnosed, untreated, biopsy-proven CD20 positive diffuse large B-cell lymphoma (DLBCL)
- Age ≥18yo and ≤80yo at the time of signing consent
- International Prognostic Index (IPI) score 0-1
- ECOG 0-2
- Have measurable disease on a pre-chemotherapy PET/CT, defined as at least one bi-dimensionally measurable nodal lesion of >1.5cm in longest dimension, or at least one bi-dimensionally measurable extranodal lesion of >1.0cm in longest dimension
- Life expectancy greater than or equal to (>/=)12 months
- Left ventricular ejection fraction (LVEF) >/= 50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
- Adequate hematologic function
- Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from donating eggs.
- Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm.
- Patients with central nervous system or primary mediastinal lymphoma, and patients with transformed lymphoma.
- Patients with uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, severe infectious diseases, etc.
- Pregnant or lactating women.
- Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV; positive by RNA polymerase chain reaction [PCR]) infection.
- Patients with concurrent other tumors or a history of tumors, or who have received anti-tumor treatment (including major surgery) within the last 4 weeks.
- Allergic reactions to polatuzumab vedotin.
- Other conditions where the investigator deems the patient ineligible for this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4×Pola-RCHP followed by 2×Pola-R Polatuzumab Vedotin Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 4 cycles. This Pola-RCHP regimen is repeated for 4 cycles, followed by 2 cycles of Polatuzumab Vedotin and Rituximab. 4×Pola-RCHP followed by 2×Pola-R Rituximab Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 4 cycles. This Pola-RCHP regimen is repeated for 4 cycles, followed by 2 cycles of Polatuzumab Vedotin and Rituximab. 4×Pola-RCHP followed by 2×Pola-R Cyclophosphamide Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 4 cycles. This Pola-RCHP regimen is repeated for 4 cycles, followed by 2 cycles of Polatuzumab Vedotin and Rituximab. 4×Pola-RCHP followed by 2×Pola-R Doxorubicin Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 4 cycles. This Pola-RCHP regimen is repeated for 4 cycles, followed by 2 cycles of Polatuzumab Vedotin and Rituximab. 4×Pola-RCHP followed by 2×Pola-R Prednisone Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 4 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 4 cycles. This Pola-RCHP regimen is repeated for 4 cycles, followed by 2 cycles of Polatuzumab Vedotin and Rituximab. 6×Pola-RCHP Polatuzumab Vedotin Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 6 cycles. This regimen is repeated for 6 cycles 6×Pola-RCHP Rituximab Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 6 cycles. This regimen is repeated for 6 cycles 6×Pola-RCHP Cyclophosphamide Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 6 cycles. This regimen is repeated for 6 cycles 6×Pola-RCHP Doxorubicin Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 6 cycles. This regimen is repeated for 6 cycles 6×Pola-RCHP Prednisone Participants will receive: Polatuzumab Vedotin: 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of every cycle for 6 cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) IV on Day 1 of every cycle for 6 cycles. Cyclophosphamide: 750 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Doxorubicin: 50 mg/m\^2 IV on Day 1 of every cycle for 6 cycles. Prednisone: 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of each 21-day cycle for 6 cycles. This regimen is repeated for 6 cycles
- Primary Outcome Measures
Name Time Method Complete response rate (CR) up to the end of 6 cycles of treatment (each cycle is 28 days)] To assess the complete response rate (CR) at the end of treatment with Treatment
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) up to 2 years The time from the enrollment of a subject to the occurrence of (in any way) progression of disease or Death for any reason. patients with indeterminate recurrence or Death at the last follow-up, defined as the date of the last Investigation
To identify biomarkers up to 2 years To identify biomarkers that may predict response to a combination regimen, biomarkers associated with progression to a more severe disease state, biomarkers that are sensitive to the development of Adverse event, biomarkers that provide evidence of the activity of the combination, or biomarkers that may enhance the understanding or understanding of the biology of the disease.
Overall Response Rate (ORR) up to the end of 6 cycles of treatment (each cycle is 28 days) Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment
Duration of Response (DoR) up to 2 years The length of time between the achievement of criteria for response to treatment (first documented complete or partial response) and the first documented relapse or progression.
Trial Locations
- Locations (1)
China Institute of Hematology and Blood Diseases Hospital
🇨🇳Tianjin, China
China Institute of Hematology and Blood Diseases Hospital🇨🇳Tianjin, ChinaLiang HuangContact13971600192huangliang@ihcams.ac.cn