Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter's Transformation

NCT05672173 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 22040NCI-2022-10247P30CA033572
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well adding lisocabtagene maraleucel (liso-cel) to nivolumab and ibrutinib works in treating patients with Richter's transformation. Liso-cel is in a class of medications called autologous cellular immunotherapy, a type of medication prepared by using cells from patient's own blood. It works by causing the body's immune system (a group of cells, tissues, and organs that protects the body from attack by bacteria, viruses, cancer cells and other substances that cause disease) to fight the cancer cells. Nivolumab is in a class of medications called monoclonal antibodies. It works by helping the immune system to slow or stop the grown of cancer. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Giving ibrutinib and nivolumab with Liso-cel may kill more cancer cells in patients with Richter's transformation.

Conditions

Refractory Transformed Chronic Lymphocytic Leukemia; Richter Syndrome; Recurrent Transformed Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR)

  After cycle 3, the rate and associated 95% binomial exact confidence interval will be estimated.

  Up to 2 years

• Unacceptable Toxicity (UT)

  Toxicities will be summarized by organ, severity, time of onset and characteristic. UT will be described individually and summarized by count and rate/percentage.

  Up to 28 days post CAR T cell infusion

Secondary Outcomes (7)

• Toxicity

  Up to 2 years

• Best Complete Response (CR)

  Up to 2 years

• Overall Response Rate (ORR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

• Minimal Residual Disease (MRD)

  Up to 2 years

Study Arms (1)

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

EXPERIMENTAL

Patients receive ibrutinib PO, nivolumab IV, fludarabine IV, cyclophosphamide IV, and liso-cel IV on study. Patients also undergo apheresis, PET/CT, biospecimen collection, and bone marrow biopsy on study. Patients may receive low-moderate intensity chemotherapy in combination with the study induction therapy per treating physician discretion with approval of study principal investigator.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Ibrutinib; Biological: Lisocabtagene Maraleucel; Biological: Nivolumab; Procedure: Pheresis; Procedure: Positron Emission Tomography

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Biospecimen Collection PROCEDURE

Undergo blood specimen collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and/or aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Lisocabtagene Maraleucel BIOLOGICAL

Given IV

Also known as: Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017, Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017, Breyanzi, JCAR 017, JCAR017

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Pheresis PROCEDURE

Undergo apheresis

Also known as: Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (nivolumab, ibrutinib, chemotherapy, liso-cel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant
• Agreement for confirmatory pre-treatment tumor biopsy
• If a patient does not have an easily accessible lymph node to biopsy without excessive risk in the opinion of the investigator, archival biopsy material reviewed by a hematopathologist at the enrolling site for study eligibility and baseline correlatives may be acceptable with approval from the Study principal investigator (PI)
• Age: \>= 18 years
• Eastern cooperative oncology group (ECOG) \<= 2
• Histologically confirmed Richter's Transformation (RT)
• Relapsed / refractory following \>=2 prior lines of systemic therapy; OR refractory to first-line chemoimmunotherapy; OR relapsed within 12 months of first line chemoimmunotherapy; OR relapsed after first line of chemoimmunotherapy and not eligible for hematopoietic stem cell transplantation due to comorbidities or age
• Eligible to receive liso-cel and ibrutinib per package inserts
• Fully recovered from the acute toxic effects (except alopecia) to \<= Grade 1 to prior anti-cancer therapy
• Absolute neutrophil count (ANC) \>= 750/mm\^3 unless there is bone marrow involvement
• Platelets \>= 75,000/mm\^3 unless there is bone marrow involvement
• Total bilirubin =\< 1.5 X ULN (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) =\< 2.5 x ULN
• Alanine aminotransferase (ALT) =\< 2.5 x ULN
• Creatinine clearance of \>= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula

You may not qualify if:

• Subjects who previously received PD1 or PD-L1 inhibitor therapy
• Autologous stem cell transplant within 3 months prior to Day 1 of protocol therapy
• Allogeneic stem cell transplant within 3 months prior to Day 1 of protocol therapy and no active graft versus host disease (GVHD) or need for immunosuppressants
• Chemotherapy, radiation therapy, immunotherapy within 14 days prior to Day 1 of protocol therapy
• Strong CYP3A inducers within 14 days prior to Day 1 of protocol therapy
• Warfarin within 5 days prior to Day 1 of protocol therapy
• Current requirement for oxygen supplementation
• Subjects with lymphoma only involving the central nervous system
• Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
• Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
• Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
• Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to screening
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for \>= 3 years

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Interventions

Biopsy; Specimen Handling; Cyclophosphamide; fludarabine; ibrutinib; Nivolumab; Blood Component Removal; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Tanya Siddiqi

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: June 2, 2023
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): September 10, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (2)