NCT05432635

Brief Summary

This phase I trial studies the safety and side effects of cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T-cells along with the CMV-modified vaccinia Ankara (MVA) triplex vaccine following a stem cell transplant in treating patients with high grade B-cell non-Hodgkin lymphoma. 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 a chimeric antigen receptor (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 following a stem cell transplant may help prevent the cancer from coming back.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
32mo left

Started Aug 2023

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress51%
Aug 2023Dec 2028

First Submitted

Initial submission to the registry

June 21, 2022

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 27, 2022

Completed
1.1 years until next milestone

Study Start

First participant enrolled

August 1, 2023

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 7, 2028

Expected
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2028

Last Updated

February 23, 2026

Status Verified

February 1, 2026

Enrollment Period

4.6 years

First QC Date

June 21, 2022

Last Update Submit

February 20, 2026

Conditions

B-Cell Non-Hodgkin LymphomaDiffuse Large B-Cell LymphomaMantle Cell LymphomaRecurrent B-Cell Non-Hodgkin LymphomaRecurrent Diffuse Large B-Cell LymphomaRecurrent Mantle Cell LymphomaRecurrent Transformed Non-Hodgkin LymphomaTransformed Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Incidence of adverse events

    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from data obtained at each clinical assessment. 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 15 years

Secondary Outcomes (5)

  • Achievement of proposed 10Ă—10^6 cytomegalovirus (CMV)-specific CD19-chimeric antigen receptor (CAR) T cells per product and meeting product release requirements for enrolled participants

    Up to 56 days

  • Short- and long-term CMV-specific CD19-CAR T cell expansion and persistence

    Up to 15 years

  • Clinically significant CMV reactivation

    Up to 15 years

  • Progression-free survival (PFS)

    From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years

  • Overall survival (OS)

    From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years

Study Arms (1)

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

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive standard conditioning regimen (typically carmustine, etoposide, cytarabine, melphalan) beginning approximately on day -9 in the absence of disease progression or unacceptable toxicity. TRANSPLANTATION: Patients undergo autoHSCT on day -2. CAR T-CELLS AND VACCINATION: Patients 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 disease progression or unacceptable toxicity.

Biological: Anti-CD19-CAR CMV-specific T-lymphocytesProcedure: Autologous Hematopoietic Stem Cell TransplantationBiological: Multi-peptide CMV-Modified Vaccinia Ankara VaccineProcedure: Myeloablative Conditioning

Interventions

Anti-CD19-CAR CMV-specific T-lymphocytesBIOLOGICAL

Given IV

Also known as: CMV-specific CD19-CAR T Cells (SY); CMV-specific CD19 CAR-T Cells (SY); Anti-CD19-CAR CMV-specific T-cells (SY)
Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)
Autologous Hematopoietic Stem Cell TransplantationPROCEDURE

Undergo autoHSCT

Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)
Multi-peptide CMV-Modified Vaccinia Ankara VaccineBIOLOGICAL

Given IM

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

Given standard conditioning regimen

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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 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 with an indication to be considered for HSCT, who are diagnosed with intermediate or high-grade B cell NHL (e.g., diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\], or transformed NHL) in first relapse after achieving complete remission (CR) or did not achieve CR after a first line therapy
  • 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 myeloablative HSCT, leukapheresis, steroids or tocilizumab, smallpox vaccine and any other modified vaccinia Ankara (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 limits of normal (ULN)
  • +11 more criteria

You may not qualify if:

  • Prior autologous/allogeneic stem cell transplant
  • 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 myeloablative HSCT 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 cells \[WBC\] / mm\^3 and no blasts in cerebrospinal 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-Cell

Interventions

Bone Marrow Purging

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Blood Component RemovalTherapeutics

Study Officials

  • Alex Herrera

    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

June 21, 2022

First Posted

June 27, 2022

Study Start

August 1, 2023

Primary Completion (Estimated)

March 7, 2028

Study Completion (Estimated)

December 30, 2028

Last Updated

February 23, 2026

Record last verified: 2026-02

Locations

US(1)