Actively Recruiting
Phase 2 Study of Lisocabtagene Maraleucel with Nivolumab and Ibrutinib for Treating Richter's Transformation
Led by City of Hope Medical Center · Updated on 2025-12-15
20
Participants Needed
2
Research Sites
N/A
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research investigates the effects of combining lisocabtagene maraleucel (liso-cel), nivolumab, and ibrutinib in treating patients with Richter's transformation, a type of aggressive lymphoma. Liso-cel is a personalized cellular immunotherapy made from the patient's own blood cells to boost the immune system's ability to fight cancer. Nivolumab is a monoclonal antibody that helps slow or stop cancer growth, and ibrutinib is a kinase inhibitor that blocks cancer cell multiplication. The trial focuses on evaluating this combination in patients who have relapsed or refractory disease after previous treatments. Participants receive the study drugs: oral ibrutinib, intravenous nivolumab, fludarabine, cyclophosphamide, and liso-cel. They also undergo procedures including apheresis to collect blood cells, PET/CT scans, blood sample collection, and bone marrow biopsy. Some patients may receive low to moderate intensity chemotherapy alongside this treatment based on the physician's discretion. The study includes a safety lead-in phase to monitor early toxicities and evaluates response rates after the third treatment cycle. During the trial, patients are regularly assessed through imaging, biopsies, and blood tests to monitor cancer response and safety. Researchers measure outcomes such as complete response rate, overall response, duration of response, minimal residual disease, progression-free survival, and overall survival over a two-year period. Safety is closely monitored, especially the rate of unacceptable toxicities within the first 28 days after liso-cel infusion. The study involves follow-up visits for up to two years to assess long-term effects and treatment outcomes.
CONDITIONS
Brief Title
Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter's Transformation
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide documented informed consent
- Agree to a pre-treatment tumor biopsy or provide an archival biopsy with approval
- Be 18 years of age or older
- Have ECOG performance status of 2 or less
- Have histologically confirmed Richter's Transformation
- Have relapsed or refractory disease after at least 2 prior systemic treatments or meet specified refractory/relapse conditions
- Be eligible to receive liso-cel and ibrutinib according to package guidelines
- Fully recovered from acute toxic effects (except alopecia) of prior anti-cancer therapy to Grade 1 or less
- Have absolute neutrophil count (ANC) of 750/mm³ or higher unless bone marrow involved
- Have platelet count of 75,000/mm³ or higher unless bone marrow involved
- Have total bilirubin less than or equal to 1.5 times upper limit normal unless Gilbert's disease
- Have AST and ALT less than or equal to 2.5 times upper limit normal
- Have creatinine clearance of 30 mL/min or higher
- Have INR or prothrombin time less than or equal to 1.5 times upper limit normal
- Have activated partial thromboplastin time less than or equal to 1.5 times upper limit normal
- Have left ventricular ejection fraction of 40% or higher within 28 days prior to treatment
- Be seronegative for Hepatitis C, active Hepatitis B, and syphilis or have undetectable viral loads if positive
- Meet institutional and federal infectious disease testing requirements
- Women of childbearing potential must have a negative pregnancy test
- Agree to use effective birth control or abstain during the study through 5 months after last dose
You will not qualify if you...
- Previous treatment with PD1 or PD-L1 inhibitors
- Autologous stem cell transplant within 3 months prior to treatment
- Allogeneic stem cell transplant within 3 months prior to treatment unless no active GVHD or immunosuppressants needed
- Chemotherapy, radiation, or immunotherapy within 14 days prior to treatment
- Use of strong CYP3A inducers within 14 days prior to treatment
- Use of warfarin within 5 days prior to treatment
- Current need for oxygen supplementation
- Use of systemic steroids or chronic immunosuppressants (except specific allowed uses)
- Lymphoma involving only the central nervous system
- Class III/IV cardiovascular disability per NYHA
- Unstable or significant arrhythmia within 2 weeks of screening
- History of optic neuritis or central nervous system inflammatory diseases
- Allergic reactions to similar compounds
- Known bleeding disorders or hemophilia
- Stroke or intracranial hemorrhage within 6 months prior to screening
- History of other malignancies except certain treated cancers without active disease
- Clinically significant uncontrolled illness
- Active infection requiring antibiotics
- Known HIV infection
- Pregnant or breastfeeding women
- Active or suspected autoimmune disease except certain controlled conditions
- Any condition judged unsafe by the investigator
- Inability to comply with study procedures due to feasibility or logistics
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 28 days or until completion of treatment cycles
Participants receive oral ibrutinib, intravenous nivolumab, intravenous fludarabine, intravenous cyclophosphamide, and intravenous lisocabtagene maraleucel (liso-cel). Participants also undergo apheresis, PET/CT scans, blood specimen collection, and bone marrow biopsy as part of the treatment process. Some participants may receive low to moderate intensity chemotherapy alongside study treatments based on physician discretion.
Multiple visits including apheresis, drug infusions, and assessments during treatment
Duration - Up to 2 years
Participants are monitored for safety, response to treatment, disease progression, and survival for up to 2 years after treatment.
Regular visits for assessments during follow-up period
Trial Site Locations
Total: 2 locations
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
2
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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