RECRUITING

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

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Conditions

Recurrent Transformed Chronic Lymphocytic LeukemiaRefractory Transformed Chronic Lymphocytic LeukemiaRichter Syndrome

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 2 Study of the Combination of Lisocabtagene Maraleucel, Nivolumab, and Ibrutinib in Richter's Transformation

Quick Facts

Study Start:2023-06-02
Study Completion:2025-09-10
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05672173

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant
  2. * Agreement for confirmatory pre-treatment tumor biopsy
  3. * 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)
  4. * Age: \>= 18 years
  5. * Eastern cooperative oncology group (ECOG) \<= 2
  6. * Histologically confirmed Richter's Transformation (RT)
  7. * 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
  8. * Eligible to receive liso-cel and ibrutinib per package inserts
  9. * Fully recovered from the acute toxic effects (except alopecia) to \<= Grade 1 to prior anti-cancer therapy
  10. * Absolute neutrophil count (ANC) \>= 750/mm\^3 unless there is bone marrow involvement
  11. * Platelets \>= 75,000/mm\^3 unless there is bone marrow involvement
  12. * Total bilirubin =\< 1.5 X ULN (unless has Gilbert's disease)
  13. * Aspartate aminotransferase (AST) =\< 2.5 x ULN
  14. * Alanine aminotransferase (ALT) =\< 2.5 x ULN
  15. * Creatinine clearance of \>= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  16. * International Normalized Ratio (INR) OR Prothrombin (PT) =\< 1.5 x ULN
  17. * Activated Partial Thromboplastin Time (aPTT) =\< 1.5 x ULN
  18. * Left ventricular ejection fraction (LVEF) \>= 40%
  19. * Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  20. * Seronegative for HCV\*, active HBV (Surface Antigen Negative), and syphilis (RPR)
  21. * If positive, Hepatitis C RNA quantitation must be performed OR
  22. * If seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  23. * Meets other institutional and federal requirements for infectious disease titer requirements
  24. * Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
  25. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  26. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  27. * Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months after the last dose of protocol therapy
  28. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  1. * Subjects who previously received PD1 or PD-L1 inhibitor therapy
  2. * Autologous stem cell transplant within 3 months prior to Day 1 of protocol therapy
  3. * 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
  4. * Chemotherapy, radiation therapy, immunotherapy within 14 days prior to Day 1 of protocol therapy
  5. * Strong CYP3A inducers within 14 days prior to Day 1 of protocol therapy
  6. * Warfarin within 5 days prior to Day 1 of protocol therapy
  7. * Current requirement for oxygen supplementation
  8. * Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone =\< 7.5 mg /day or equivalent) is allowed throughout the study. Use of "bridging" steroids, to control disease, after leukapheresis and until 3 days prior to CAR T cell infusion, is allowed
  9. * Subjects with lymphoma only involving the central nervous system
  10. * Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
  11. * Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
  12. * 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
  13. * Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  14. * Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  15. * History of stroke or intracranial hemorrhage within 6 months prior to screening
  16. * 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
  17. * Clinically significant uncontrolled illness
  18. * Active infection requiring antibiotics
  19. * Known history of immunodeficiency virus (HIV)
  20. * Females only: Pregnant or breastfeeding
  21. * Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment, well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible
  22. * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  23. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Tanya Siddiqi
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Tanya Siddiqi, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-02
Study Completion Date2025-09-10

Study Record Updates

Study Start Date2023-06-02
Study Completion Date2025-09-10

Terms related to this study

Additional Relevant MeSH Terms

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