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

NCT06441097 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: GUIDANCE-005
• Study Type: interventional
• Target: 152
• Locations: 0 countries
• Sites: N/A

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 2 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 Acalabrutinib 100 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: Acalabrutinib; 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

Acalabrutinib DRUG

Acalabrutinib 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 Acalabrutinib/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
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible
• Participants with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
• Participants receiving adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer for ≥ 2 years prior to enrollment are eligible
• Participants with any other malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment are eligible
• 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
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
• \- Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits, as judged by the investigator, are allowed
• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
• History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
• \- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 4 weeks before the start of Cycle 1
• Active autoimmune disease which is not well controlled by therapy

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; acalabrutinib; 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: May 26, 2024
• First Posted: June 4, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 4, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share