Diffuse Large B-Cell Lymphoma
Conditions
Interventions
Experimental group:Glofitamab in combination with Polatuzumab Vedotin plus Rituximab, Cyclophosphamide, Doxorubicin,and Prednisone (Pola-R-CHP)
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form. 2. Age 18–75 years at the time of signing the informed consent form and willingness to comply with study procedures. 3. Treatment-naïve subjects with CD20-positive large B-cell lymphoma (LBCL). 4. International Prognostic Index (IPI) score of 2–5. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3. 6. Life expectancy >= 6 months. 7. Presence of at least one bidimensionally measurable lesion, defined as a lesion with the longest diameter > 1.5 cm as measured by PET/CT, CT, or MRI. 8. Left ventricular ejection fraction (LVEF) >= 50% as measured by echocardiogram (ECHO). 9. Adequate hematologic function defined as: ? Hemoglobin >= 9.0 g/dL without red blood cell transfusion within 7 days prior to infusion. ? Absolute neutrophil count (ANC) >= 1.0 × 10^9/L. ? Platelet count >= 75 × 10^9/L. 10. Negative HIV test result at screening. 11. For female subjects of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods. 12. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods. 13. Subjects must meet either the ctDNA kinetics or PET2-positivity criteria (fulfill one of the following): Assessed as ctDNA high-risk (less than 2-log reduction in ctDNA at the start of Cycle 2). Interim PET scan at the end of Cycle 2 of Pola-R-CHP assessed using the Deauville 5-Point Scale (DS), with a positive criterion of DS 4–5.
Exclusion criteria
Exclusion criteria: 1. Contraindication to any individual component of Pola-R-CHP or glofitamab, history of severe or anaphylactic allergic reactions, known sensitivity, or allergy to murine products. 2. History of solid organ transplantation. 3. Central nervous system (CNS) involvement. 4. Current peripheral neuropathy > Grade 1. 5. History of indolent lymphoma. 6. Prior therapy for LBCL, except corticosteroids (e.g., >10 mg/day prednisone or equivalent) used for purposes other than controlling lymphoma symptoms. 7. History of other malignancy that could affect protocol compliance or interpretation of results. ? Subjects with a history of curatively treated cutaneous basal or squamous cell carcinoma, melanoma, or carcinoma in situ of the cervix at any time prior to the study are eligible. ? Subjects with low-grade, early-stage prostate cancer (Gleason score =2 years for non-metastatic, hormone receptor-positive breast cancer prior to enrollment are eligible. ? Subjects with any other appropriately treated malignancy with curative intent, which has been in remission without treatment for >=2 years prior to enrollment, are eligible. 8. Significant or extensive history of cardiovascular disease, such as New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction within 6 months prior to Cycle 1 Day 1, unstable arrhythmias, or unstable angina. 9. Major surgery within 28 days prior to Cycle 1 Day 1, except for diagnostic surgery. 10. Current or prior history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. ? Subjects with a history of stroke with no residual neurological deficits are eligible. Transient ischemic attacks within the past 2 years without residual deficits may be allowed per investigator's judgment. 11. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: ? Poorly controlled active autoimmune disease. ? Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. ? Subjects with controlled Type 1 diabetes mellitus on an insulin regimen are eligible. 12. Any of the following abnormal laboratory values (unless attributable to underlying lymphoma): ? INR or PT > 1.5 × ULN without anticoagulation; aPTT > 1.5 × ULN. ? Serum AST and ALT >= 2.5 × ULN. ? Total bilirubin >= 1.5 × ULN. ? Subjects with documented Gilbert's syndrome may be enrolled if total bilirubin is <= 3.0 × ULN. ? Estimated creatinine clearance < 40 mL/min (using Cockcroft-Gault formula). 13. Any active infection within 7 days prior to Cycle 1 Day 1 that may compromise subject safety. ? Known active bacterial, viral, fungal, mycobacterial, parasitic, or other significant infection (excluding fungal infections of nail beds) at study enrollment. ? Positive test for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology). ? Positive test for hepatitis C (hepatitis C virus [HCV] antibody serology). 14. Pregnancy, lactation, or intention to become pregnant during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete remission rate, CRR; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate, ORR;Duration of complete remission, DOCR ;Overall survival, OS;Progression free survival, PFS;safety ;Duration of relief, DOR; | — |
Countries
China
Contacts
Public ContactDanbin Zhou, Yan Zhang
Peking Union Medical College Hospital
Outcome results
None listed