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

NCT06516978 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 2024-SR-436
• Study Type: interventional
• Target: 528
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 24 months (PFS24) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma

  At 24 months

Secondary Outcomes (5)

• Complete Response Rate (CRR) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma

  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

  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

  up to approximately 48 months

• Overall Survival (OS)

  up to approximately 48 months

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From enrollment to study completion, a maximum of 48 months

Study Arms (3)

Pola-RCHP-X

EXPERIMENTAL

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

RCHOP-X

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Orelabrutinib; Drug: Venetoclax; Drug: Chidamide; Drug: Penpulimab; Drug: Lenalidomide

Pola-RCHP

ACTIVE COMPARATOR

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: Polatuzumab vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Interventions

Polatuzumab vedotin DRUG

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

Pola-RCHP; Pola-RCHP-X

Rituximab DRUG

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

Pola-RCHP; Pola-RCHP-X; RCHOP-X

Cyclophosphamide DRUG

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

Pola-RCHP; Pola-RCHP-X; RCHOP-X

Doxorubicin DRUG

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

Pola-RCHP; Pola-RCHP-X; RCHOP-X

Vincristine DRUG

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

RCHOP-X

Prednisone DRUG

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

Pola-RCHP; Pola-RCHP-X; RCHOP-X

Orelabrutinib DRUG

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

Pola-RCHP-X; RCHOP-X

Venetoclax DRUG

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

Pola-RCHP-X; RCHOP-X

Chidamide DRUG

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

Pola-RCHP-X; RCHOP-X

Penpulimab DRUG

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

Pola-RCHP-X; RCHOP-X

Lenalidomide DRUG

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

Pola-RCHP-X; RCHOP-X

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; orelabrutinib; venetoclax; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; penpulimab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Central Study Contacts

Wei Xu

CONTACT

+8602568306034; xuwei10000@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: July 24, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: July 24, 2024

Record last verified: 2024-07