Efficacy and Safety of Pola-RCHP-X vs Pola-RCHP in Untreated DLBCL

NCT06803693 | Recruiting Phase 2

• 1 other identifier: GUIDANCE05
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the efficacy and safety of genotype-guided targeted agents in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola RCHP-X) versus Pola RCHP in Chinese patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival（by IRC）

  PFS, defined as the time from randomization to the first occurrence of disease progression or relapse using the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first; as determined by the investigator

  From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)

Secondary Outcomes (6)

• Progression-free survival（by the investigator）

  From randomization to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)

• Event-free survival

  up to approximately 24 months

• Complete response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Objective response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Overall survival

  up to approximately 3 years

Study Arms (2)

Pola-RCHP-X

EXPERIMENTAL

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day2, rituximab 375 milligrams per square meter (mg/m²) IV on Day 1, cyclophosphamide 750 mg/m² IV on Day 2， doxorubicin 50 mg/m² IV on Day 2 and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 2-6 of every 21-day cycle for the first cycle. For the remaining 5 cycles, they will receive Zanubrutinib 160 mg BID PO on days 1-21, or lenalidomide 25 mg/day PO on days 1-10, or decitabine 10 mg/m²/day IV on days -5 to -1 followed by standard Pola-RCHP of every 21-day cycle.

Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Zanubrutinib; Drug: Lenalidomide; Drug: Decitabine

Pola-RCHP

ACTIVE COMPARATOR

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV) on Day2, rituximab 375 milligrams per square meter (mg/m²) IV on Day 1, cyclophosphamide 750 mg/m² IV on Day 2， doxorubicin 50 mg/m² IV on Day 2 and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 2-6 of every 21-day cycle for 6 cycles.

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

Cyclophosphamide DRUG

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

Pola-RCHP; Pola-RCHP-X

Doxorubicin DRUG

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

Pola-RCHP; Pola-RCHP-X

Prednisone DRUG

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

Pola-RCHP; Pola-RCHP-X

Zanubrutinib DRUG

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

Pola-RCHP-X

Lenalidomide DRUG

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

Pola-RCHP-X

Decitabine DRUG

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

Pola-RCHP-X

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age 18-75 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
• Previously untreated participants with CD20-positive DLBCL
• IPI score 2-5
• ECOG Performance Status of 0, 1, or 2
• After 1 cycle of Pola-R-CHP, ctDNA decreased by \< 3.0 LFC
• Life expectancy ≥ 6 months
• 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 Zanubrutinib/Lenalidomide/ Decitabine
• Prior solid organ transplantation or SCT
• Current diagnosis of the following: Follicular lymphoma grade 3B; mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; PCNSL
• 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 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 \< 30 mL/min (using Cockcroft-Gault formula)
• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology)：Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HbsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing every month and appropriate antiviral therapy as indicated
• Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)：Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA
• Participants with a history of progressive multifocal leukoencephalopathy
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 months after final dose of Pola-RCHP-X
• Other concurrent and uncontrolled medical conditions that, in the opinion of the investigator, would affect the patient's participation in the study

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; zanubrutinib; Lenalidomide; Decitabine

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; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; zwl_trial@163.com

Pengpeng Xu

CONTACT

+862164370045; pengpeng_xu@126.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: January 27, 2025
• First Posted: January 31, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)