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

July 18, 2024 updated by: WEI XU, The First Affiliated Hospital with Nanjing Medical University

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

528

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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: Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
Drug: Lenalidomide
Lenalidomide 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: Polatuzumab vedotin
Polatuzumab vedotin IV infusion 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.
Active Comparator: 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.
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: Prednisone
Prednisone PO 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: Lenalidomide
Lenalidomide 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.
Active Comparator: 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.
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: Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
Drug: Polatuzumab vedotin
Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival at 24 months (PFS24) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma
Time Frame: At 24 months
At 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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]
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]
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
up to approximately 48 months
Overall Survival (OS)
Time Frame: up to approximately 48 months
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
From enrollment to study completion, a maximum of 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2024

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

July 18, 2024

First Submitted That Met QC Criteria

July 18, 2024

First Posted (Actual)

July 24, 2024

Study Record Updates

Last Update Posted (Actual)

July 24, 2024

Last Update Submitted That Met QC Criteria

July 18, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-SR-436

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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