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

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Not yet enrolling; Phase 2

Conditions: DLBCL - Diffuse Large B Cell Lymphoma

Treatments: Drug: Rituximab; Drug: Prednisone; Drug: Polatuzumab Vedotin; Drug: Doxorubicin; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT07034508

IIT2025053

Details and patient eligibility

About

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

Full 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.

Enrollment: 134 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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134 participants in 2 patient groups

4×Pola-RCHP followed by 2×Pola-R

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Polatuzumab Vedotin

Drug: Prednisone

Drug: Rituximab

6×Pola-RCHP

Active Comparator group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Polatuzumab Vedotin

Drug: Prednisone

Drug: Rituximab