Polatuzumab Vedotin and Zanubrutinib Plus R-CHP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Safety Issues Clinical Trial

Official title:

Polatuzumab Vedotin and Zanubrutinib Plus R-CHP for Patients in Treatment of Newly Diagnosed Untreated Non-GCB DLBCL With Extranodal Involvement.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06468943
• Other study ID #: Pola-ZR-CHP
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: May 1, 2028

Study information

• Verified date: April 2024
• Source: The First Affiliated Hospital of Soochow University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim of this study will evaluate the efficacy and safety of Polatuzumab Vedotin and Zanubrutinib in combination with R-CHP for newly diagnosed untreated Non-GCB DLBCL Patients with extranodal involvement.

Description:

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of DLBCL was non-GCB subtype DLBCL.The non-GCB DLBCL revealed poor clinical outcomes. Bruton's tyrosine kinase (BTK) inhibitors have established therapeutic activity in B cell malignancies, with potential activity in non-GCB DLBCL. The POLARIX study also observed an benefit in the efficacy of Polatuzumab Vedotin in first-line treatment of DLBCL patients. This study will evaluate the efficacy and safety of Polatuzumab Vedotin and Zanubrutinib in combination with R-CHP for newly diagnosed untreated Non-GCB DLBCL Patients with extranodal involvement.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: May 1, 2028
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL with extrinsic involvement;

2. Measurable disease of at least 15mm(node)/10mm(extranodal);

3. ECOG performance status 0-2;

4. Adequate organ function:Cardiac ejection fraction (EF) = 50%;Creatinine clearance rate (=30 mL/min) of serum creatinine; Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) =3 times ULN;

5. Adequate bone marrow function:Platelet count (= 50×10^9/L);Hemoglobin (= 8 g/dL);The absolute value of neutrophils (=1.0×10^9/L)

6. Estimated survival time =3 months

7. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study.

Exclusion Criteria:

1. Accepted major surgery within 4 weeks before treatment;

2. Diagnosis of primary mediastinal lymphoma or primary CNS lymphoma;

3. Previous history of indolent lymphoma;

4. Prior malignancy (other than DLBCL), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer ?malignant tonsilloma or carcinoma in situ;

5. History of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists;

6. Requires treatment with a strong/medium CYP3A inducer;

7. The previous use of anthracycline-based drugs > 150 mg/m2;

8. Evidence of complications or medical conditions, including but not limited, that may interfere the conduct of the study or place the patient at serious risk:significant cardiovascular disease(class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification?myocardial infarction within 6 months of screening?uncontrolled or symptomatic arrhythmias) and/or significant lung disease;

9. HIV infection and/or active hepatitis B or active hepatitis C;

10. Uncontrolled systemic infection;

11. Pregnant or breasting-feeding women;

12. According to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.

Related Conditions & MeSH terms

• Effects of Chemotherapy
• Safety Issues

Intervention

Drug:
• Polatuzumab Vedotin
1.8mg/kg/21d(d0) Intravenous infusion
• Zanubrutinib
160mg bid PO(d0-d20)
• Rituximab
375mg/?/21d(d0) Intravenous infusion
• Cyclophosphamide
750mg/?/21d(d1) Intravenous infusion
• Doxorubicin
50mg/?/21d(d1) Intravenous infusion
• Prednisone
100mg PO (d1-d5)/21d

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Nanjing

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory study endpoint	Exploring the therapeutic response of subjects with different genotypes to Pola+ZR-CHP regimen using Next-generation sequencing(NGS).	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.
Primary	Progression-free Survival(PFS)	The time between enrollment and tumor occurrence (in any aspect) progression or (for any reason) death	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.
Secondary	Objective Response rate(ORR)	The proportion of patients who achieved complete or partial response in efficacy evaluation at the end of treatment	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.
Secondary	Complete Response(CR)	The proportion of patients who achieved complete response in efficacy evaluation at the end of treatment	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.
Secondary	Duration of Response(DOR)	It refers to the time from the first assessment of a tumor as CR or PR to the second assessment as PD (Progressive Disease) or death from any cause.	All time in the study
Secondary	Overall Survival	The time between enrollment to death(for any reason) .	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.
Secondary	Adverse Events(AEs)	All treatment-related adverse events that occur during patient treatment and follow-up.	From date of enrollment until the date follow up for 2 years after the treatment or progression disease or date of death for any cause.