RECRUITING

Genetically Modified T-cells (CMV-Specific CD19-CAR T-cells) Plus a Vaccine (CMV-MVA Triplex) for the Treatment of Intermediate or High Grade B-Cell Non-Hodgkin Lymphoma

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Conditions

High Grade B-Cell Non-Hodgkin's LymphomaIntermediate Grade B-Cell Non-Hodgkin's LymphomaRecurrent B-Cell Non-Hodgkin LymphomaRefractory B-Cell Non-Hodgkin 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 studies the safety and feasibility of cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T cells in combination with the CMV-modified vaccinia Ankara (MVA) triplex vaccine following lymphodepletion in treating patients with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refectory). CAR T cells are a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added in the laboratory. The special receptor is called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Vaccines such as CMV-MVA triplex are made from gene-modified viruses and may help the body build an effective immune response to kill cancer cells. Giving CMV-specific CD19-CAR T-cells plus the CMV-MVA triplex vaccine may help prevent the cancer from coming back.

Official Title

A Pilot / Feasibility Study of Autologous CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine in Patients With Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma

Quick Facts

Study Start:2023-09-29
Study Completion:2028-12-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05801913

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 and/or legally authorized representative
  2. * Assent, when appropriate, will be obtained per institutional guidelines
  3. * Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  4. * If unavailable, exceptions may be granted with study principal investigator (PI) approval
  5. * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed
  6. * Age: \>= 18 years
  7. * Karnofsky Performance Status (KPS) \>= 70
  8. * Life expectancy \>= 16 weeks at the time of enrollment
  9. * Patients requiring treatment for relapsed or refractory intermediate or high-grade B cell NHL (e.g., diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\], or transformed NHL) who are not eligible for, or who refuse, or have previously received autologous hematopoietic cell transplantation (autoHCT)
  10. * Note: COH pathology review should confirm that research participant's diagnostic material is consistent with history of intermediate or high-grade CD19+ malignancy
  11. * No known contraindications to leukapheresis, lymphodepleting chemotherapy, steroids or tocilizumab, smallpox vaccine and any other MVA-based vaccines
  12. * Patient must be CMV seropositive
  13. * Total serum bilirubin =\< 2.0 mg/dL
  14. * Participants with Gilbert syndrome may be included if their total bilirubin is =\< 3.0
  15. * Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
  16. * Alanine aminotransferase (ALT) \< 2.5 x ULN
  17. * Serum creatinine =\< 2.5 x ULN or estimated creatinine clearance of \>= 40 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis
  18. * Absolute neutrophil count \>= 1000/uL (Transfusions and growth factors must not be used to meet these requirements at initial screening)
  19. * Hemoglobin (Hb) \>= 8 g/dl (Transfusions and growth factors must not be used to meet these requirements at initial screening)
  20. * Platelet count \>= 50,000/uL (\>= 30,000/uL if bone marrow plasma cells are \>= 50% of cellularity) (Transfusions and growth factors must not be used to meet these requirements at initial screening)
  21. * Left ventricular ejection fraction \>= 45% within 8 weeks before enrollment
  22. * Oxygen (O2) saturation \> 92% without requiring supplemental oxygen
  23. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  24. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  25. * 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 6 months after the last dose of protocol therapy
  26. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  1. * Prior allogeneic stem cell transplant unless the participant has recovered from transplantation and does not have active graft versus host disease (GVHD)
  2. * Growth factors within 14 days of enrollment
  3. * Platelet transfusions within 7 days of enrollment
  4. * Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =\< 5 mg/day, or equivalent doses of other corticosteroids) is allowed
  5. * Patients with active autoimmune disease requiring systemic immune suppressive therapy are not allowed
  6. * Participants may not be receiving any other investigational agents or concurrent biological therapy, chemotherapy, or radiation therapy
  7. * Any standard contraindications to lymphodepleting chemotherapy and/or CAR T-cell therapy per standard of care practices at COH
  8. * Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
  9. * Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system (CNS), including seizure disorder, any measurable masses of CNS, or any other active CNS disease
  10. * Note: Research participants with a history of CNS disease that has been effectively treated to complete remission (\< 5 white blood cell \[WBC\]/mm\^3 and no blasts in cerebral spinal fluid \[CSF\]) will be eligible
  11. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents or cetuximab
  12. * Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  13. * History of stroke or intracranial hemorrhage within 6 months prior to screening
  14. * 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
  15. * Clinically significant uncontrolled illness
  16. * Active infection requiring antibiotics
  17. * Immunodeficiency virus (human immunodeficiency virus \[HIV\]) positive
  18. * Active viral hepatitis
  19. * Females only: Pregnant or breastfeeding
  20. * Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
  21. * 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

Leslie L Popplewell
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

  • Leslie L Popplewell, 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 Date2023-09-29
Study Completion Date2028-12-30

Study Record Updates

Study Start Date2023-09-29
Study Completion Date2028-12-30

Terms related to this study

Additional Relevant MeSH Terms

  • High Grade B-Cell Non-Hodgkin's Lymphoma
  • Intermediate Grade B-Cell Non-Hodgkin's Lymphoma
  • Recurrent B-Cell Non-Hodgkin Lymphoma
  • Refractory B-Cell Non-Hodgkin Lymphoma