None listed
Conditions
Interventions
Drug : 1. Obinutuzumab
- obinutuzumab 1000 mg pretreatment will be administered intravenously on Day 1 of Cycle 1
2. Glofitamab
- Glofitamab will be administered on a step-up dosing schedule star
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed informed consent form. 2) Age = 19 years at the time of signing the informed consent form. 3) Histologically diagnosed diffuse large B-cell lymphoma, NOS initially, as defined by 2016 WHO guidelines and confirmed relapsed and refractory disease, defined as follows. - Relapsed: the disease that has recurred following a response that lasted over 6 months after completing the last line of therapy. - Refractory: the disease that did not respond to or that progressed less than 6 months after completion of the last line of therapy. 4) RR-DLBCL patients who should undergo CD 19 CAR-T cell treatment prior to recruitment of this study have achieved partial response (PR) one or three months after CAR-T cell infusion. - If the patient achieves PR at one or three months, patients have to enroll within at least 3 months after CAR-T cell infusion. 5) ECOG PS: 0-2 6) Adequate hematologic function, as defined by the following laboratory values (If cytopenia is associated with bone marrow involvement, the subject is excluded): - Absolute neutrophil > 1,000/mm3 - Hemoglobin > 9.0 g/dL (Transfusion free within 21 days prior to administration of glofitamab) - Platelet > 75,000/mm3 (Transfusion free within 21 days prior to administration of glofitamab) - If the patient does not recover neutropenia at one month even though achieving CR or PR, the investigator could wait until 3 months from first achieving CR or PR at one month. However, the patient has to remain in CR or PR status. 7) Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment 8) Adequate organ function, as defined by the following laboratory values - AST, ALT 1,000/mm3 - Hemoglobin > 9.0 g/dL (Transfusion free within 21 days prior to administration of glofitamab) - Platelet > 75,000/mm3 (Transfusion free within 21 days prior to administration of glofitamab) - If the patient does not recover neutropenia at one month even though achieving CR or PR, the investigator could wait until 3 months from first achieving CR or PR at one month. However, the patient has to remain in CR or PR status. 7) Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment 8) Adequate organ function, as defined by the following laboratory values - AST, ALT < 3.0x upper limit of normal (ULN). - Total bilirubin < 1.5 X ULN(patients with a documented history of Gilbert’s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible if the total bilirubin is <3x ULN) - Serum creatinine = 1.5 mg/dL, Creatinine clearance = 50ml/min. 9) Female subjects are required to meet the following criteria: - Pregnancy test: For women of childbearing potential, a negative serum or urine pregnancy test at screening - Contraception: Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of < 1% per year from screening until at least 3 months after pre-treatment with obinutuzumab, 2 months after the last dose of glofitamab, 2 months after the last dose of tocilizumab (if applicable), whichever is longer, if the patient is a male. If the patient is a female, effective contraception should be used
Exclusion criteria
Exclusion criteria: 1) Patients have failed to achieve PR at 1 month or 3 months after CD19 CAR-T cell therapy. 2) Patients who received previously treated bispecific antibodies. 3) Current or past history of primary or secondary central nervous system (CNS) lymphoma. 4) Peripheral neuropathy was assessed to be grade >1 according to NCI CTCAE v5.0 at enrollment. 5) Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. - Patients with a history of stroke who have not experienced a stroke of transient ischemic attack within the past 2 years and have no residual neurologic deficits, as judged by the investigator, are allowed. 6) Any of the following abnormal laboratory values, unless abnormal laboratory values are associated with the underlying lymphoma per the investigator. (Patients with a documented history of Gilbert’s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible if the total bilirubin is = 3 × ULN) - AST/ALT = 3.0 x upper limit of normal (ULN). - Total bilirubin = 1.5.0 X ULN. 7) Has a concomitant malignancy or had a malignancy (except for appropriately treated basal or squamous cell carcinoma or cervical carcinoma in situ) in the last 3 years prior to initiation of the study treatment 8) Underwent a major surgery within 21 days prior to initiating the study treatment or has not recovered from severe side effects of surgery 9) Concomitant use of immunosuppressants, except for the following: - Intranasal, inhaled, or topical steroid, or local steroid injection (such as intra-articular injection) - Physiological dose = 10 mg/day of prednisone or equivalent doses of systemic corticosteroid. - Premedication with steroids to prevent hypersensitivity reaction (such as premedication prior to a CT scan). At the discretion of the investigator, the use of prednisolone at =10 mg for adrenal insufficiency may be acceptable. 10) Clinically significant or active cardiovascular disease - Myocardial infarction: within 6 months prior to study entry - Unstable angina, congestive heart failure (New York Heart Association class =III) or Objective Assessment Class C or D cardiac disease, or serious cardiac arrhythmias requiring medication, including any of the following: ? Left ventricular ejection fraction (LVEF) 480 msec (using the QTcF formula) on ECG at screening, ? unstable angina, ? ventricular arrhythmias except for benign premature ventricular contractions, ? medically uncontrolled supraventricular and nodal arrhythmias, ? conduction abnormality requiring a pacemaker, ? valve disease with documented cardiac dysfunction 11) Other concomitant severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, chronic pancreatitis, active chronic hepatitis, etc.) that the investigator considers would preclude the subject's participation in the clinical trial. - Other severe acute or chronic medical conditions include colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, or psychiatric conditions, including recent (in the last 1 year) or active suicidal thoughts or behaviors; or laboratory abnormalities that, in the investigator's opinion, may increase the risk associated with participation in the clinical trial or study treatment, or that may interfere with the interpretation of clinical trial results. results. 12) Active infection or rea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response | — |
Secondary
| Measure | Time frame |
|---|---|
| progression free survival | — |
Countries
Korea, Republic of
Contacts
Public ContactJayeon Kim
Samsung Medical Center
Outcome results
None listed