Relapsed or Refractory Large B-Cell Lymphoma
Conditions
Interventions
Experimental group:Glofitamab + Gemcitabine + Oxaliplatin
Control group:Standard salvage chemotherapy (like ICE, DHAP, etc.), and if remission is achieved, then continue with autologous stem cell transplant (ASCT)
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Sign the informed consent form; 2. Be at least 18 years old when signing the informed consent form and willing to follow the study protocol; 3. Histologically confirmed LBCL; 4. Relapsed or refractory disease after first-line immunochemotherapy: (1) Refractory disease is defined as not achieving complete remission with first-line treatment; participants intolerant to first-line treatment are excluded: 1) Best response to first-line treatment is progressive disease (PD); 2) Best response is stable disease (SD) after at least 3-4 cycles of first-line treatment; 3) Best response is partial remission (PR) after at least 6-8 cycles, or disease progression occurs within = 12 weeks; 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 8. CT scan shows at least one measurable (>=1.5 cm) nodal lesion or one measurable (>=1 cm) extranodal lesion; 9. HIV test is negative at screening. 10. Adequate hematologic function (unless impaired due to underlying conditions, such as extensive bone marrow involvement or investigator-assessed hypersplenism secondary to DLBCL spleen involvement), defined as: (1) Hemoglobin >= 9.0 g/dL without red blood cell transfusion within 7 days prior to initial treatment (2) Absolute neutrophil count (ANC) = 1.0 x 10^9/L (3) Platelet count >= 75 x 10^9/L 11. Adequate organ function, defined as: (1) Creatinine clearance (estimated by Cockcroft-Gault formula) >= 60 mL/min (2) Serum ALT/AST 50%, no evidence of pericardial effusion on echocardiogram, and no clinically significant ECG abnormalities (5) No clinically significant pleural effusion (6) Baseline oxygen saturation in room air > 92% 12. Able to understand and complete study-related questionnaires; 13. For female participants of childbearing potential: agree to remain abstinent (avoid sexual intercourse with males) or use contraception, and agree not to donate eggs, defined as follows: (1) Women must remain abstinent or use a contraceptive method with a failure rate of less than 1% during treatment and for at least 18 months after the last dose of ocrelizumab, 12 months after the last dose of rituximab, 6 months after the last dose of gemcitabine, 9 months after the last dose of oxaliplatin, 4 months after the last dose of tocilizumab, and 4 months after the last dose of gefitinib. (2) Female participants are considered of childbearing potential if they have had their first period, are not postmenopausal (>=12 consecutive months without menstruation, with no other definite causes besides menopause), and are not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or other reasons determined by the investigator (e.g., Mayer-Rokitansky-Küster-Hauser syndrome). (3) According to this definition, female participants with tubal ligation are considered of childbearing potential. (4) The definition of childbearing potential may be adjusted according to local guidelines or regulations. (5)
Exclusion criteria
Exclusion criteria: 1. Any contraindications to glofitamab, or a history of severe allergy or hypersensitivity to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products; 2. Participants not eligible for ASCT; 3. Prior solid organ transplant; 4. History of Richter transformation or indolent disease transforming to DLBCL or primary mediastinal large B-cell lymphoma (PMBCL); 5. At enrollment, peripheral neuropathy above grade 1 as assessed by NCI CTCAE v5.0; 6. Previous treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3; 7. Any investigational therapy for lymphoma within 28 days before starting cycle 1; 8. Prior radiation therapy to the mediastinal/pericardial area (1) Radiation to non-target lesions is allowed; 9. History of autologous or allogeneic stem cell transplant; 10. Adverse events from previous anticancer treatments have not resolved to grade 1 or better (except hair loss and anorexia); 11. Have received more than one line of therapy for DLBCL; 12. Using more than 50 mg/day of prednisone or an equivalent dose of corticosteroids for purposes other than controlling lymphoma symptoms: (1) Participants receiving up to 50 mg/day of prednisone or an equivalent corticosteroid dose for reasons other than controlling lymphoma symptoms (e.g., rheumatoid arthritis) must have been on a stable dose for at least 4 weeks before the start of Cycle 1. 1) Corticosteroids can be used to manage cancer symptoms or side effects from previous treatments (e.g., nausea or B symptoms). 2) Inhaled corticosteroids are allowed. 3) Mineralocorticoids can be used for orthostatic hypotension. 4) Physiologic doses of corticosteroids can be used to treat adrenal insufficiency. (2) Participants who need to control lymphoma symptoms during the screening period can use steroids as follows: 1) During screening (including before final staging), up to 50 mg/day of prednisone or an equivalent dose can be used to control lymphoma symptoms (not as part of prior therapy). 2) If higher doses of glucocorticoids are urgently needed before starting study treatment to control lymphoma symptoms, a tumor assessment must be completed before starting more than 30–100 mg/day of prednisone or equivalent. 3) More than 30–100 mg/day of prednisone or equivalent can be given as prior therapy for a maximum of 10–14 days. 4) Vincristine should not be used as part of prior therapy. 13. Major surgery other than diagnostic procedures within the 4 weeks before first study treatment. 14. Other cancer history that may affect protocol compliance or result interpretation: (1) Participants with a history of treated skin basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ at any time before the study are eligible. (2) Participants with any malignancy that has been appropriately treated and in remission for =2 years before enrollment without needing treatment are eligible – participants with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) that doesn’t require treatment at any time before the study are eligible. 15. A history of severe or extensive cardiovascular disease, such as NYHA Class III or IV heart disease or objectively assessed Class C or D, myocardial infarction, unstable arrhythmia, or unstable angina within 3 months before the start of cycle 1. 16. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disorders – partici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Complete Response rate; | — |
Countries
China
Contacts
Public ContactChangju Qu
The First Affiliated Hospital of Soochow University
Outcome results
None listed