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

NCT ID: NCT06516978

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 528 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2029-04-01

Brief Summary

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.

Conditions

Diffuse Large B Cell Lymphoma

Study Design

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

Study Groups

Pola-RCHP-X

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.

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.

Orelabrutinib

Intervention Type: DRUG

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

Venetoclax

Intervention Type: DRUG

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

Chidamide

Intervention Type: DRUG

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

Penpulimab

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

RCHOP-X

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.

Group Type: ACTIVE_COMPARATOR

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.

Vincristine

Intervention Type: DRUG

Vincristine 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.

Orelabrutinib

Intervention Type: DRUG

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

Venetoclax

Intervention Type: DRUG

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

Chidamide

Intervention Type: DRUG

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

Penpulimab

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Pola-RCHP

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.

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

Vincristine

Vincristine 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

Orelabrutinib

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

Intervention Type: DRUG

Venetoclax

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

Intervention Type: DRUG

Chidamide

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

Intervention Type: DRUG

Penpulimab

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

Intervention Type: DRUG

Lenalidomide

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

Intervention Type: DRUG

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

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

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

WEI XU

M.D

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Wei Xu

Role: CONTACT

xuwei10000@hotmail.com

+8602568306034

Other Identifiers

2024-SR-436

Identifier Type: -

Identifier Source: org_study_id