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

NCT05801913 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22459NCI-2023-02195P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 28 days

• 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.

  Up to 15 years

Secondary Outcomes (6)

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

  Up to 56 days

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

  Up to 15 years

• Clinically significant CMV reactivation

  Up to 15 years

• Disease response (complete response/minor response/partial response/disease progression/stable disease)

  28 and 84 days after CAR T cell infusion

• Progression-free survival

  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

Study Arms (1)

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

EXPERIMENTAL

Patients 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.

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

Interventions

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Leukapheresis PROCEDURE

Undergo leukapheresis per SOC

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Lymphodepletion Therapy PROCEDURE

Undergo lymphodepletion chemotherapy per SOC

Also known as: Lymphodepleting Therapy, Lymphodepletion

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

X-Ray Imaging PROCEDURE

Undergo x-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiography, RG, Static X-Ray, X-Ray

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Anti-CD19-CAR CMV-specific T-lymphocytes BIOLOGICAL

Given IV

Also known as: Anti-CD19-CAR CMV-specific T-cells, CMV-specific CD19 CAR-T Cells, CMV-specific CD19-CAR T Cells

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Specimen Handling; Biopsy; Leukapheresis; Magnetic Resonance Spectroscopy; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Leslie L Popplewell

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 6, 2023
• Study Start: September 29, 2023
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)