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

Official title

A Prospective, Open-Label, Multicenter, Randomized Controlled Study Comparing 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 Diffuse Large B-Cell Lymphoma

Overview

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.

Interventions

• Drug Polatuzumab vedotin
  Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Rituximab
  Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Cyclophosphamide
  Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Doxorubicin
  Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Vincristine
  Vincristine IV infusion will be administered as per the schedule specified in the respective arm.
• Drug Prednisone
  Prednisone PO will be administered as per the schedule specified in the respective arm.
• Drug Orelabrutinib
  Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
• Drug Venetoclax
  Venetoclax PO will be administered as per the schedule specified in the respective arm.
• Drug Chidamide
  Chidamide PO will be administered as per the schedule specified in the respective arm.
• Drug Penpulimab
  Penpulimab IV infusion will be administered as per the schedule specified in the respective arm.

Primary outcome measures

• Progression Free Survival at 24 months (PFS24) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma [Time frame: At 24 months]

Secondary outcome measures (5)

• Complete Response Rate (CRR) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days]]
• Overall Response Rate (ORR) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days]]
• Event Free Survival (EFS) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma [Time frame: up to approximately 48 months]
• Overall Survival (OS) [Time frame: up to approximately 48 months]
• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From enrollment to study completion, a maximum of 48 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06516978 · 2024-SR-436

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗