None listed
Conditions
Brief summary
What the study is about: This study aims to find out whether a short course of the medicines polatuzumab vedotin (PV) and rituximab, with or without targeted radiotherapy, can better control lymphoma while patients wait for their personalised CAR-T cell therapy with Tisa-cel. Many people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have fast-growing disease, and some may become too unwell to receive CAR-T treatment during the manufacturing period. Early control of the lymphoma during this waiting time—called bridging therapy—may help improve the chances that CAR-T therapy works well. Who is this trial for: • 18 years of age or older with a prior diagnosis of DLBCL, • Have had the cancer return after two or more treatments, • You are eligible to receive CAR-T cell treatment and have already had leukapheresis. Study Details: This is a single arm, open label, phase 2 study. Participants will receive bridging therapy before CAR-T cell treatment with: • Polatuzumab vedotin (PV) administered intravenous (IV) on Day 1. • Rituximab administered IV on Day 1. • Depending on the wait time for Tisa-cel manufacture, a 2nd dose of PV and rituximab can be administered on day 22. • Radiotherapy may be added if your doctor recommends it. This study will recruit a total 47 participants across Australia, Taiwan, Hong Kong, and South Korea. What is hoped from it: This trial will help determine whether a more effective and tolerable bridging strategy can keep patients well enough for CAR-T therapy and improve their long-term outcomes.
Interventions
Participants will receive bridging therapy prior to Tisa-cell CAR-T cell treatment with:
• Polatuzumab vedotin (1.8mg/kg) administered intravenous (IV) on Day 1 before Rituximab administration.
• Rituximab (375mg/m^2) administered IV on Day 1.
• Both medicines will be administered 3 weeks prior to Tisa-cell CAR-T cell treatment. A second dose of both medicines may be administered on Day 21 at physician's discretion. 2 doses is the maximum number in bridging therapy.
• Radiotherapy may be add
Participants will receive bridging therapy prior to Tisa-cell CAR-T cell treatment with: • Polatuzumab vedotin (1.8mg/kg) administered intravenous (IV) on Day 1 before Rituximab administration. • Rituximab (375mg/m^2) administered IV on Day 1. • Both medicines will be administered 3 weeks prior to Tisa-cell CAR-T cell treatment. A second dose of both medicines may be administered on Day 21 at physician's discretion. 2 doses is the maximum number in bridging therapy. • Radiotherapy may be added at physician's discretion from Day 1 of bridging therapy and completed 7-10 days before chemotherapy lymphodepletion of Tisa-cell CAR-T cell treatment. All treatment will be administered by the study team (i.e., registered nurse, the lead physician, physicians listed on the trial to assist the lead physician). Drug accountability will be performed by the administering institutions to assess compliance through pharmacy dispensing logs, dose administration records, and verifying patient diaries.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All of the following criteria must be satisfied for enrolment in the study. 1. Aged greater or equal to18 years at the time of signing the informed consent form. 2. Histologically confirmed Diffuse Large B Cell Lymphoma (DLBCL) (including transformed follicular lymphoma, transformed marginal zone lymphoma, or high-grade B-cell lymphoma with specified rearrangements of myc and bcl-2). 3. Relapsed or refractory disease after two or more prior lines of systemic therapy. 4. Planned treatment with commercial Tisa-cel, and is scheduled for leukapheresis (trial registration will require patient to have had leukapheresis performed) . 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Screening 6. Adequate bone marrow function defined as: a. Absolute neutrophil count (ANC) greater or equal to1.0×10^9/L. b. Platelet count greater or equal to 75×10^9/L (or greater or equal to 50×10^9/L in the presence of bone marrow involvement). c. Hemoglobin greater or equal to 8.0 g/dL (may be maintained by transfusion). 7. Adequate organ function defined as: a. Total bilirubin level less or equal to 2× upper limit of normal (ULN) (unless due to Gilbert's syndrome or lymphoma involvement). b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less or equal to 5× ULN (or less or equal to 5× ULN if due to hepatic involvement of disease). c. Creatinine clearance greater or equal to 40 mL/min, by estimated Glomerular Filtration Rate (eGFR) of Cockcroft-Gault formula. d. Left ventricular ejection fraction greater or equal to40% determined by Echocardiogram or MUGA and no clinically significant abnormal electrocardiogram (ECG) findings. e. Baseline oxygen saturation greater than 91% on room air. 8. At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. 9. Toxicities due to prior therapy must be stable and recovered to Grade less or equal to 1 or baseline (except for clinically nonsignificant toxicities such as alopecia). 10. Females of childbearing potential must use an effective method of contraception or practice absolute abstinence for 4 weeks prior to therapy, during treatment and at least 6 months after treatment discontinuation. 11. Male patients must use contraception measures 1 week prior to commenced of study drug, during treatment with study drug and at least 6 months after discontinuation of treatment.
Exclusion criteria
Presence of any of the following criteria will exclude the subject from enrolment in the study. 1. Patients with primary refractory Diffuse Large B Cell Lymphoma (DLBCL). 2. Not eligible for Standard-of-care Tisa-cel therapy 3. Any contraindications to polatuzumab vedotin. 4. Known history of severe allergic or anaphylactic reactions to any component of polatuzumab vedotin, Rituximab, lymphodepletion chemotherapy (cyclophosphamide or fludarabine), or prior intolerance to the planned radiotherapy 5. Known active bacterial, viral, fungal, mycobacterial, or other infection History of Human Immunodeficiency Virus (HIV) infection or acute or chronic active hepatitis B or C infection. Subjects with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing. 6. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g.: cervical, bladder, breast) unless disease free for at least 3 years or considered to be at low risk of progression in the subsequent 5 years. 7. Prior CD19-targeted antibody unless lymphoma biopsy is shown to express CD19 at the time of screening. 8. History or presence of a clinically significant central nervous system (CNS) disorder, such as cerebrovascularischemia/hemorrhage, dementia, or any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema with confirmed structural defects by appropriate imaging. 9. Patients with seizure disorders requiring active anticonvulsive medication. Note: Prior or active CNS involvement by lymphoma is not an exclusion criterion, unless uncontrolled 10. History of stroke or transient ischemic attack within 12 months before screening 11. History of unstable angina, myocardial infarction, congestive heart failure, New York Heart Association (NYHA) Class III or IV), severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 12 months of screening. 12. Active autoimmune disease requiring immunosuppression within 2 years prior to screening. 13. Rapidly progressive lymphoma kinetics – patient likely to have uncontrolled/rapidly progressing disease for the duration of manufacturing. 14. Live vaccine of less or equal to 6 weeks before planned start of lymphodepletion therapy 15. Active, uncontrolled graft-versus-host disease grade 2 or above, or with ongoing need for Graft vs Host Disease (GVHD) therapy. 16. Pregnant or breastfeeding females, or subjects (male or female) of childbearing potential who are unwilling to use a highly effective method of contraception for the duration of the study and for at least 12 months after the last dose of study drug. 17. Concurrent treatment with another CD19-targeting investigational drug or participation in another lymphoma drug or regime or therapeutic clinical study within 30 days or 5 half-lives of the drug (s) (whichever is longer) prior to commencement of bridging therapy
Outcome results
None listed