Actively Recruiting
A Pilot Study of Autologous CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine for Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma
Led by City of Hope Medical Center · Updated on 2026-03-05
15
Participants Needed
1
Research Sites
39 weeks
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying a new treatment approach for patients with intermediate or high-grade B-cell non-Hodgkin lymphoma (NHL) that has returned after improvement or does not respond to treatment. This phase I trial evaluates the safety and feasibility of using genetically modified T cells called CMV-specific CD19-CAR T cells combined with a CMV-modified vaccinia Ankara (MVA) triplex vaccine. The treatment aims to engage the immune system to attack cancer cells and prevent the cancer from coming back. Patients first undergo a procedure called leukapheresis about 30 days before treatment to collect T cells, followed by lymphodepleting chemotherapy from days -10 to -3 according to standard care. On day 0, patients receive an infusion of the modified T cells intravenously. They then receive the CMV-MVA triplex vaccine by intramuscular injection on days 28 and 56, provided there are no serious side effects. The study includes a dose-escalation phase followed by a dose-expansion phase to evaluate treatment effects. Throughout the study, participants will have various assessments including X-rays during screening and treatment, as well as PET, CT, and MRI scans, blood tests, and bone marrow biopsies. Researchers will monitor safety and side effects up to 15 years, measure T cell levels and disease responses at 28 and 84 days, and track survival and cancer progression over time. The total involvement includes initial treatment and long-term follow-up to assess the treatment's effects and safety.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participant or legally authorized representative has provided documented informed consent
- Agreement to allow use of archival tissue from diagnostic tumor biopsies or approved exception
- Age 18 years or older
- Karnofsky Performance Status of 70 or higher
- Life expectancy of at least 16 weeks at enrollment
- Diagnosis of relapsed or refractory intermediate or high-grade B-cell NHL who are not eligible for or refuse autologous hematopoietic cell transplantation
- No contraindications to leukapheresis, lymphodepleting chemotherapy, steroids, tocilizumab, smallpox vaccine, or MVA-based vaccines
- Positive for cytomegalovirus (CMV) antibodies
- Total serum bilirubin less than or equal to 2.0 mg/dL (up to 3.0 mg/dL if Gilbert syndrome present)
- AST and ALT less than 2.5 times upper limit of normal
- Serum creatinine less than or equal to 2.5 times upper limit of normal or creatinine clearance of at least 40 mL/min, not on hemodialysis
- Absolute neutrophil count of at least 1000/uL without recent transfusions or growth factors
- Hemoglobin of at least 8 g/dL without recent transfusions or growth factors
- Platelet count of at least 50,000/uL (or at least 30,000/uL if bone marrow plasma cells are 50% or more) without recent transfusions or growth factors
- Left ventricular ejection fraction of at least 45% within 8 weeks prior to enrollment
- Oxygen saturation over 92% without supplemental oxygen
- Women of childbearing potential must have a negative pregnancy test and agree to use birth control or abstain from heterosexual activity during the study and for 6 months after last dose
- Agreement by males of childbearing potential to use effective birth control or abstain from heterosexual activity during the same period
You will not qualify if you...
- Prior allogeneic stem cell transplant without full recovery and absence of active graft versus host disease
- Use of growth factors within 14 days prior to enrollment
- Platelet transfusions within 7 days prior to enrollment
- Concurrent systemic steroids or chronic immunosuppressant use (except low-dose physiologic replacement)
- Active autoimmune disease requiring systemic immune suppression
- Receiving other investigational agents or concurrent biological therapy, chemotherapy, or radiation
- Contraindications to lymphodepleting chemotherapy or CAR T-cell therapy
- Clinically significant unstable arrhythmias within 2 weeks of screening
- History of optic neuritis or other active immunologic/inflammatory CNS disease, except treated CNS disease in remission
- Allergic reactions to similar compounds or cetuximab
- Known bleeding disorders like von Willebrand's disease or hemophilia
- Stroke or intracranial hemorrhage within 6 months prior to screening
- Other malignancies except those treated with curative intent and no active disease for 3 or more years
- Clinically significant uncontrolled illness
- Active infection requiring antibiotics
- HIV positive
- Active viral hepatitis
- Pregnant or breastfeeding females
- Any condition that contraindicates study participation due to safety concerns
- Inability to comply with study procedures due to logistical or feasibility issues
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) including x-ray imaging
Duration - Approximately 27 days
Participants undergo leukapheresis and receive lymphodepleting chemotherapy per standard of care before treatment.
1 leukapheresis visit and multiple visits for lymphodepleting chemotherapy over days -10 to -3
Duration - Up to 56 days
Participants receive CMV-specific CD19-CAR T cells intravenously and CMV-MVA triplex vaccine intramuscularly if no unacceptable toxicity occurs.
1 day 0 visit for CAR T cell infusion and 2 vaccine visits on days 28 and 56
Duration - Up to 15 years
Participants undergo imaging, blood sample collection, and bone marrow biopsy to assess safety, disease response, and cell persistence.
Multiple imaging and sample collection visits during treatment and follow-up
Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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