A Phase II Trial of 4 vs 6 Cycles of CHP Combined With Polatuzumab Vedotin-Rituximab in Untreated DLBCL Patients With IPI 0-1

NCT ID: NCT07034508

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-20
• Study Completion Date: 2029-12-20

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.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

4×Pola-RCHP followed by 2×Pola-R

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.

Group Type: EXPERIMENTAL

Polatuzumab Vedotin

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

6×Pola-RCHP

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

Group Type: ACTIVE_COMPARATOR

Polatuzumab Vedotin

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Interventions

Polatuzumab Vedotin

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

China Institute of Hematology and Blood Diseases Hospital

Tianjin, , China

Countries

China

Central Contacts

Liang Huang

Role: CONTACT

huangliang@ihcams.ac.cn

13971600192

Facility Contacts

Liang Huang

Role: primary

huangliang@ihcams.ac.cn

13971600192

Other Identifiers

IIT2025053

Identifier Type: -

Identifier Source: org_study_id