NCT05801913 · City of Hope Medical Center
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
What this study is about
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.
View original scientific 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.
Interventions
BIOLOGICAL
Anti-CD19-CAR CMV-specific T-lymphocytes
Given IV
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
PROCEDURE
Bone Marrow Biopsy
Undergo bone marrow biopsy
PROCEDURE
Computed Tomography
Undergo CT
PROCEDURE
Leukapheresis
Undergo leukapheresis per SOC
PROCEDURE
Lymphodepletion Therapy
Undergo lymphodepletion chemotherapy per SOC
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
BIOLOGICAL
Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
Given IM
PROCEDURE
Positron Emission Tomography
Undergo PET
PROCEDURE
X-Ray Imaging
Undergo x-ray
Primary outcome measures
Incidence of dose-limiting toxicity
Time frame: Up to 28 days
Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0, and the revised American Society for Transplantation and Cellular Therapy (ASTCT) cytokine release syndrome (CRS) grading systems. Will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Incidence of adverse events
Time frame: Up to 15 years
Will be assessed and graded according to the NCI CTCAE v5.0, and the ASTCT consensus grading for CRS and neurotoxicity associated with immune effector cells.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principal investigator (PI) approval
- 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
- Age: \>= 18 years
- Karnofsky Performance Status (KPS) \>= 70
- Life expectancy \>= 16 weeks at the time of enrollment
- 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)
- Note: COH pathology review should confirm that research participant's diagnostic material is consistent with history of intermediate or high-grade CD19+ malignancy
- No known contraindications to leukapheresis, lymphodepleting chemotherapy, steroids or tocilizumab, smallpox vaccine and any other MVA-based vaccines
- Patient must be CMV seropositive
- Total serum bilirubin =\< 2.0 mg/dL
- Participants with Gilbert syndrome may be included if their total bilirubin is =\< 3.0
- Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) \< 2.5 x ULN
- 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
- Absolute neutrophil count \>= 1000/uL (Transfusions and growth factors must not be used to meet these requirements at initial screening)
- Hemoglobin (Hb) \>= 8 g/dl (Transfusions and growth factors must not be used to meet these requirements at initial screening)
- 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)
- Left ventricular ejection fraction \>= 45% within 8 weeks before enrollment
- Oxygen (O2) saturation \> 92% without requiring supplemental oxygen
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- 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
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion criteria
- Prior allogeneic stem cell transplant unless the participant has recovered from transplantation and does not have active graft versus host disease (GVHD)
- Growth factors within 14 days of enrollment
- Platelet transfusions within 7 days of enrollment
- 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
- Patients with active autoimmune disease requiring systemic immune suppressive therapy are not allowed
- Participants may not be receiving any other investigational agents or concurrent biological therapy, chemotherapy, or radiation therapy
- Any standard contraindications to lymphodepleting chemotherapy and/or CAR T-cell therapy per standard of care practices at COH
- 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 (CNS), including seizure disorder, any measurable masses of CNS, or any other active CNS disease
- 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents or cetuximab
- 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
- Clinically significant uncontrolled illness
- Active infection requiring antibiotics
- Immunodeficiency virus (human immunodeficiency virus \[HIV\]) positive
- Active viral hepatitis
- Females only: Pregnant or breastfeeding
- 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
- 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)
Where
- Duarte, California
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 5, 2026 · Source of record for eligibility and locations