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High Grade B-Cell Non-Hodgkin's LymphomaPhase 1NCT05801913

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

A Phase 1 study testing Anti-CD19-CAR CMV-specific T-lymphocytes, Biospecimen Collection and Bone Marrow Biopsy in people with High Grade B-Cell Non-Hodgkin's Lymphoma and Intermediate Grade B-Cell Non-Hodgkin's Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-CD19-CAR CMV-specific T-lymphocytes, Biospecimen Collection and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
29 Sep 2023to 30 Dec 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Leslie L. Popplewell, 626-218-2405, lpopplew@coh.org

    Leslie L. Popplewell

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Assess the safety and describe the toxicity profile of anti-CD19-CAR CMV-specific T-lymphocytes (CMV-specific CD19-CAR T cells) as monotherapy and when given in combination with a multi-peptide CMV-modified vaccinia Ankara vaccine (CMV-MVA Triplex) following standard of care lymphodepletion.

SECONDARY OBJECTIVES:

  1. Determine the feasibility of autologous CMV-specific CD19-CAR T cell manufacturing, as assessed by the ability to meet the required cell dose and product release requirements.

II. Estimate the overall and complete disease response rate at days 28 and 84 after CAR T cell infusion.

III. Determine short- and longer-term CMV-specific CD19-CAR T cell in vivo expansion and persistence.

IV. Assess whether the CMV-specific CD19-CAR T cells respond to CMV-MVA Triplex vaccine.

  1. Estimate the rate of CMV reactivation after CAR T cell. VI. Estimate the one-year progression-free survival (PFS) rate and median overall survival (OS) post-CAR T cell infusion.

EXPLORATORY OBJECTIVE:

  1. Assess whether the CMV-specific CD19-CAR T cells respond to CMV-MVA Triplex vaccine when administered to participants that received CAR T cells only in the safety lead-in portion in the expansion phased of the study (i.e., once safety of the CMV-MVA Triplex vaccine is established in the feasibility portion of the study).

OUTLINE: This is a dose-escalation study of CMV-specific CD19-CAR T cells followed by a dose-expansion study.

Patients undergo leukapheresis on day -30 and receive lymphodepleting chemotherapy on days -10 to -3 per standard of care (SOC) on study. Patients then receive CMV-specific CD19-CAR T cells intravenously (IV) on day 0 and CMV-MVA triplex vaccine intramuscularly (IM) on days 28 and 56 in the absence of unacceptable toxicity on study. Patients also undergo x-ray during screening and on study, as well as positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), blood sample collection, and bone marrow biopsy on study and during follow-up.

Being tested
Anti-CD19-CAR CMV-specific T-lymphocytes, Biospecimen Collection, Bone Marrow Biopsy, Computed Tomography, Leukapheresis
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-CD19-CAR CMV-specific T-lymphocytesBiological

    Also called Anti-CD19-CAR CMV-specific T-cells, CMV-specific CD19 CAR-T Cells, CMV-specific CD19-CAR T Cells

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis per SOC

  • Lymphodepletion TherapyProcedure or surgery

    Also called Lymphodepleting Therapy, Lymphodepletion

    Undergo lymphodepletion chemotherapy per SOC

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • Multi-peptide CMV-Modified Vaccinia Ankara VaccineBiological

    Also called CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine

    Given IM

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo PET

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs

    Undergo x-ray

Study groups in NCT05801913
Study groupRoleWhat they receive
Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)ExperimentalPatients undergo leukapheresis on day -30 and receive lymphodepleting chemotherapy on days -10 to -3 per SOC on study. Patients then receive CMV-specific CD19-CAR T cells IV on day 0 and CMV-MVA triplex vaccine IM on days 28 and 56 in the absence of unacceptable toxicity on study. Patients also undergo x-ray during screening and on study, as well as PET, CT, MRI, blood sample collection, and bone marrow biopsy on study and during follow-up.
Receives: Biological: Anti-CD19-CAR CMV-specific T-lymphocytes; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Lymphodepletion Therapy; Procedure: Magnetic Resonance Imaging; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine; Procedure: Positron Emission Tomography; Procedure: X-Ray Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicity

    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.

    Measured: Up to 28 days

  2. Incidence of adverse events

    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.

    Measured: Up to 15 years

Secondary outcomes (6)

  1. Feasibility as assessed by the ability to meet the required cell dose and product release requirement

    Feasibility will be assessed by achieving the proposed dose of CMV-specific CD19-CAR T cells per product and meeting product release requirements for enrolled participants. The goal is to manufacture 10 x 10^6 cells (this is a flat dose).

    Measured: Up to 56 days

  2. Short- and long-term cytomegalovirus (CMV)-specific CD19-chimeric antigen receptor (CAR) T cell expansion and persistence

    Will be assessed longitudinally. Persistence is defined as detection of >= 0.1% of CMV-specific CD19-CAR T cells in CD3+ cells in peripheral blood, 28 days after vaccine administration, by flow cytometry and Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element quantitative polymerase chain reaction (Q-PCR). Expansion is defined as an increase of 2-fold in CMV-specific CD19-CAR T cells after Triplex administration compared with pre-vaccination cell number. Response to Triplex will be assessed based on numbers of EGFR+, pp65-specific interferon gamma (IFNy)+ and CD137+T cells.

    Measured: Up to 15 years

  3. Clinically significant CMV reactivation

    Clinically significant defined as > 1250 IU/ml or 500 GC/mL) CMV reactivation requiring management treatment after CAR T cell infusion as assessed by PCR.

    Measured: Up to 15 years

  4. Disease response (complete response/minor response/partial response/disease progression/stable disease)

    Will be assessed according to International Working Group consensus response evaluation criteria in lymphoma 2017. The specific time trend for CMV-specific CD19-CAR T cells will be assessed using linear mixed effects modeling. The overall fit of the model will be evaluated graphically by taking a scatter plot of data for the CAR T cells and applying an overlay of the line generated by the model. To assess changes over time, functional regression modeling will be used.

    Measured: 28 and 84 days after CAR T cell infusion

  5. Progression-free survival

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Time from the start of lymphodepletion to the time of disease relapse, progression or death, whichever occurs first, assessed at 1 year and up to 15 years

  6. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Time from the start of lymphodepletion to death, assessed up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2023
  2. Study start29 Sep 2023
  3. Primary completion30 Mar 2028 (estimated)
  4. Study completion30 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05801913
Sponsor's protocol ID
22459
Other IDs
NCI-2023-02195, 22459, P30CA033572
Status last verified
Mar 2026
First submitted
24 Mar 2023
Last updated
5 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-CD19-CAR CMV-specific T-lymphocytes, Biospecimen Collection and Bone Marrow Biopsy in people with High Grade B-Cell Non-Hodgkin's Lymphoma and Intermediate Grade B-Cell Non-Hodgkin's Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05801913.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.

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