A Study Comparing the Efficacy and Safety of Pola-RCHP-X Versus RCHOP-X and Pola-RCHP in Previously Untreated Patients With DLBCL

Nanjing Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Diffuse Large B Cell Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Chidamide; Drug: Polatuzumab vedotin; Drug: Venetoclax; Drug: Vincristine; Drug: Doxorubicin; Drug: Penpulimab; Drug: Orelabrutinib; Drug: Prednisone; Drug: Rituximab; Drug: Lenalidomide

Study type: Interventional

Funder types: Other

Identifiers

NCT06516978

2024-SR-436

Details and patient eligibility

About

This study aims to compare the efficacy and safety of Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone combined with Orelabrutinib/Chidamide/Venetoclax/Lenalidomide/PD1 (Pola-RCHP-X) versus RCHOP-X and Pola-RCHP in previously untreated patients with DLBCL.

Enrollment: 528 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Sign the informed consent form
• Previously untreated participants with CD20-positive DLBCL
• Life expectancy ≥ 6 months
• IPI score 2-5
• ECOG Performance Status of 0, 1, or 2
• Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to involvement of the spleen by DLBCL per the investigator for which blood product transfusions are permitted) defined as follows:

Hemoglobin ≥ 9.0 g/dL without packed RBC transfusion during 7 days before first treatment ANC ≥ 1.0 x 10^9/L PLT ≥ 75 x 10^9/L

Exclusion criteria

• Contraindication to any of the individual components of Pola-RCHP or Orelabrutinib/Chidamide/Venetoclax/Lenalidomide/PD1
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina
• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
• Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):

Serum AST and ALT ≥ 2.5 x ULN Total bilirubin ≥ 1.5 x ULN Serum creatinine clearance < 40 mL/min (using Cockcroft-Gault formula)

• Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
• Participants with a history of progressive multifocal leukoencephalopathy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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528 participants in 3 patient groups

Pola-RCHP-X

Experimental group

Description:

From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.

Treatment:

Drug: Lenalidomide

Drug: Penpulimab

Drug: Orelabrutinib

Drug: Prednisone

Drug: Rituximab

Drug: Doxorubicin

Drug: Venetoclax

Drug: Polatuzumab vedotin

Drug: Chidamide

Drug: Cyclophosphamide

RCHOP-X

Active Comparator group

Description:

From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.

Treatment:

Drug: Lenalidomide

Drug: Penpulimab

Drug: Orelabrutinib

Drug: Prednisone

Drug: Rituximab

Drug: Doxorubicin

Drug: Venetoclax

Drug: Vincristine

Drug: Chidamide

Drug: Cyclophosphamide

Pola-RCHP

Active Comparator group

Description:

From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.

Treatment:

Drug: Prednisone

Drug: Rituximab

Drug: Doxorubicin

Drug: Polatuzumab vedotin

Drug: Cyclophosphamide