None listed
Conditions
Interventions
Drug : 1. Initial treatment
All patients will receive 3 cycles of glofitamab + ICE
2. Interim response assessment and treatment allocation
- Interim response assessment with PET/CT and MRD will be c
D15, I.V. 10mg)
2) Glofitamab target dose (C2~4 for ASCT arm, C2~6 for no ASCT arm)
- Glofitamab: will be administered at target dose of I.V. 30mg (D1)
: Every 3 weeks
4.2 ICE (C1~4 for ASCT arm,
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed DLBCL patients with relapsed/refractory disease 2. Age of 19 to 70 years old 3. Patient is eligible for high-dose therapy and autologous stem cell transplantation 4. Subjects who have received first-line systemic therapy containing an anti-CD20 antibody and an anthracycline. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter 7 . Adequate laboratory parameters within 14 days - Absolute neutrophil count (ANC) = 1000/mm3 regardless of growth factor support - Platelets = 75,000/mm3 independent of transfusion support - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x upper limit of normal (ULN) - Total bilirubin = 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin -Estimated Glomerular Filtration Rate = 40 mL/min/1.73m2 8 . Provision of a signed written informed consent 9 . Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for at least 18 months after the last dose of study drug(s) and must have a negative urine (or serum) pregnancy test = 7 days before initial treatment. 10 . Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for at least 6 months after the last dose of study drug (a ‘sterile’ male is defined as one for whom azoospermia has been previously demonstrate in a semen sample examination as definitive evidence of infertility) *Very effective contraception • Intrauterine device • Bilateral atretic oviduct (A surgical procedure to prevent fertilization of an ovum) • Vasectomy of female subject’s male partner (Surgical success of vasectomy confirmed by medical evaluation) • Hormonal contraception associated with suppression of ovulation : Oral contraception pill (Estrogen/progestin pill or progestin alone pill), Skin contraceptive patch, intravaginal contraceptive ring, or subcutaneous contraceptive injection • Sexual abstinence (only abstinence from sexual intercourse with members of the opposite sex for the entire period of study-related risks is acceptable) 11 . Life expectancy = 6 months
Exclusion criteria
Exclusion criteria: 1. History of another primary cancer other than DLBCL, unless the subject has been free of the disease for = 3 years with the exception of the following non-invasive malignancies: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin in situ (stage 0), carcinoma in situ of the cervix, carcinoma in situ of the breast, early gastric cancer, incidental histologic finding of prostate cancer (T1a or T1b) or prostate, cancer that is curative 2. Subjects who have previously received two or more lines of systemic anticancer therapy. 3. History of autologous or allogenic stem cell transplantation 4 . Prior history of solid organ transplantation or other cause of severe immunodeficiency 5 . Intravascular DLBCL 6 . History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 7 . Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results 8 . Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis 9 . Known diagnosis of HIV infection (HIV testing is not mandatory). However, HIV+ patients with sustained negative viral load can be enrolled. 10 . Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below: • HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded. • HCV: positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded. 11 . Pregnant, breastfeeding, or possibly pregnant. 12 . Alcohol or substance abuse disorder 13 . Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3. However, patients who maintained a response for =6 months after treatment completion are eligible for enrollment in the study. 14 . Prior treatment with ifosfamide, carboplatin, or etoposide 15 . Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma. However, prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible. 16 . Clinically significant cardiovascular disease including the following: • Myocardial infarction = 6 months before screening. • Unstable angina = 3 months before screening. • New York Heart Association class 3 or 4 congestive heart failure (see Appendix F ). • History of clinically significant arrhythmia (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes). • QTcF (Fridericia’s correction) > 480 msec. • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place. • Uncontrolled hypertension as indicated by = 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mm Hg and diastolic blood pres
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CR rate after completion of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response rate (CRR);Overall response rate (ORR) ;Duration of response ;Progression-free survival ;Event-free survival (EFS);Overall survival ;Autologous stem cell transplantation (ASCT) rate ;Safety profile ;Tumor microenvironment analysis using spatial transcriptomics and peripheral immune cell profile using single cell RNA sequencing to discover potential biomarker associated ORR, CRR, PFS, EFS, and OS;Evaluation of the genomic landscape and its correlation with efficacy (ORR, CRR, PFS, EFS, OS) using whole-genome sequencing;Patient reported outcome (EORTC QLQ-C30) ;MRD negativity rate | — |
Countries
Korea, Republic of
Contacts
Public ContactDayoung Choi
Asan Medical Center
Outcome results
None listed