RECRUITING

Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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Conditions

Recurrent Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma

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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 I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.

Official Title

A Phase I Study to Evaluate the Safety of Escalating Doses of Lymphodepleting Conditioning Chemotherapy Prior to CD19 Chimeric Antigen Receptor T Cells in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Quick Facts

Study Start:2021-09-17
Study Completion:2025-12-15
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05052528

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. * Provision of signed and dated informed consent form
  2. * Stated willingness to comply with all study procedures and availability for the duration of the study
  3. * Commercial CD19 CAR T cell product not available for the patient
  4. * Male or female, aged \>= 18
  5. * In good general health as evidenced by medical history or as determined by the principal investigator (PI)
  6. * Ability to swallow oral medication and willingness to adhere to the study intervention and any required medications
  7. * For females of reproductive potential: use of highly effective contraception (oral contraceptives, intrauterine device) during screening confirmed with serum pregnancy test, and agreement to use such a method during study participation and for an additional 4 weeks after the end of CD19 CAR T cell infusion
  8. * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
  9. * Agreement to adhere to lifestyle considerations throughout study duration including abstaining from tobacco and drug use
  10. * Subjects must have relapsed or refractory diffuse large B cell lymphoma treated with at least two lines of therapy Subjects must have failed to have a complete response, or have recurrent disease after the last treatment regimen. Subjects must have previously been treated with a regimen that includes an anthracycline and an anti-CD20 monoclonal antibody. Autologous transplant will be counted as one line of therapy
  11. * The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available
  12. * Age \>= 18 years
  13. * Performance status: Adult Subjects: Eastern Cooperative Oncology Group (ECOG) \>= 1; Subjects \> 10 years of age: Karnofsky \>= 80%
  14. * Absolute neutrophil count (ANC) \>= 1000
  15. * Platelets \>= 100/mm\^3
  16. * Hemoglobin \> 8 g/dL
  17. * ANC \>= 500 is acceptable if documented bone marrow involvement by disease
  18. * Creatinine clearance (estimated by Cockcroft Gault) or using 24 hour (hr) urine collection \>= 50 cc/min
  19. * Total bilirubin =\< 2 mg/dL except in subjects with Gilbert's Syndrome in whom total bilirubin must be =\< 3.0
  20. * Alanine transaminase (alanine aminotransferase \[ALT\]/serum glutamic pyruvic transaminase \[SGPT\]) and aspartate aminotransferase (aspartate aminotransferase \[AST\]/serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x the upper limit of normal or =\< 5 x the upper limit of normal if documented liver involvement by disease
  21. * Cardiac left ventricular ejection fraction \>= 45% as determined by an echocardiogram and no clinically significant electrocardiogram (ECG) findings
  22. * Baseline oxygen saturation \> 92% on room air
  23. * Prior cancer directed therapy wash-out: at least 2 weeks or 5 half-lives, whichever is shorter must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for radiotherapy within 10 days of apheresis, systemic corticosteroid use within 7 days of apheresis (with the exception of single dose for an allergic reaction), or any other immunosuppressive therapies within 7 days
  24. * No use of lymphodepleting agents including alemtuzumab and antithymocyte globulin for 7 days prior to peripheral blood collection, 5 days prior to CD19 CAR T cell infusion and for 90 days after infusion
  1. * Presence of supplemental oxygen, cardiac pacemaker
  2. * Known allergic reactions to components of the anti-CD19 CAR T cell product as evidenced by prior documented anaphylactic reaction or other clinical signs and/or symptoms of an allergic reaction as determined by the PI
  3. * Febrile illness within 3 days of admission for lymphodepleting conditioning therapy
  4. * Treatment with another investigational drug or other investigational intervention within 2 weeks of apheresis
  5. * Primary immunodeficiency
  6. * History of autoimmune diseases (ex: Crohn's, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's) resulting in end organ damage or requiring systemic immunosuppressive or systemic disease modifying agents within the last two years prior to enrollment
  7. * Autologous transplant within 6 weeks and allogeneic transplant within 3 months of planned CAR T cell infusion
  8. * Recipient of CD19 CAR T cell therapy outside of this protocol
  9. * Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast-enhanced magnetic resonance imaging (MRI) for at least 30 days prior to study enrollment
  10. * History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast)
  11. * Active human immunodeficiency virus (HIV) infection documented by positive viral load
  12. * Subjects with uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements
  13. * Pregnant or breastfeeding women are excluded from this study because CAR T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) weeks after receiving the CAR-T cell infusion
  14. * Diagnosis of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
  15. * Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded)

Contacts and Locations

Principal Investigator

Mehrdad Abedi
PRINCIPAL_INVESTIGATOR
University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
United States

Collaborators and Investigators

Sponsor: Mehrdad Abedi, MD

  • Mehrdad Abedi, PRINCIPAL_INVESTIGATOR, University of California, Davis

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 Date2021-09-17
Study Completion Date2025-12-15

Study Record Updates

Study Start Date2021-09-17
Study Completion Date2025-12-15

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Diffuse Large B-Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma