Actively Recruiting
Pilot/Feasibility Study of CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Following Autologous Hematopoietic Stem Cell Transplantation for Patients With Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma
Led by City of Hope Medical Center · Updated on 2026-02-23
15
Participants Needed
1
Research Sites
42 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 evaluating the safety and side effects of a new treatment combining cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T-cells with a CMV-modified vaccinia Ankara (MVA) triplex vaccine after stem cell transplant in patients with intermediate or high-grade B-cell non-Hodgkin lymphoma. This phase I trial aims to assess how well these genetically modified T-cells and the vaccine work together to prevent cancer from returning. The study also examines the production feasibility, immune response, and long-term outcomes including survival and disease progression. Participants receive a standard conditioning regimen of chemotherapy drugs starting about nine days before the transplant, followed by an autologous hematopoietic stem cell transplant (autoHSCT) on day -2. On day 0, patients are given an infusion of the CMV-specific CD19-CAR T-cells intravenously. The CMV-MVA triplex vaccine is then administered intramuscularly on days 28 and 56, provided there is no disease progression or unacceptable side effects. The trial includes a safety lead-in and expansion phase to evaluate the combined treatment and vaccine effects. During the study, participants are closely monitored with follow-up visits at 18-24 hours, weekly for three weeks, at one month, day 84, monthly from months 4 to 11, and at one year post-treatment. Those with disease progression or receiving prohibited therapies have additional follow-ups up to 15 years. The research team measures adverse events, immune cell persistence, CMV reactivation, progression-free survival, and overall survival to understand the treatment's safety and potential benefits over time.
CONDITIONS
Brief Title
Genetically Modified T-cells (CMV-Specific CD19-CAR T-cells) Plus a Vaccine (CMV-MVA Triplex) Following Stem Cell Transplantation for the Treatment of Intermediate or High Grade B-cell Non-Hodgkin Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Documented informed consent from the participant or legally authorized representative
- Agreement to allow use of archival tissue from diagnostic tumor biopsies (exceptions possible with approval)
- Age 18 years or older
- Karnofsky performance status of 70 or higher
- Life expectancy of at least 16 weeks at enrollment
- Diagnosis of intermediate or high-grade B-cell non-Hodgkin lymphoma in first relapse after complete remission or without complete remission after first therapy
- No known contraindications to myeloablative stem cell transplant, leukapheresis, steroids, tocilizumab, smallpox vaccine, or MVA-based vaccines
- Participant must be CMV seropositive
- Total serum bilirubin less than or equal to 2.0 mg/dL (up to 3.0 mg/dL if Gilbert syndrome)
- AST less than 2.5 times upper limit of normal
- 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 40 mL/min or higher, not on hemodialysis
- Absolute neutrophil count 1000/uL or higher without transfusions or growth factors at screening
- Hemoglobin 8 g/dL or higher without transfusions or growth factors at screening
- Platelet count 50,000/uL or higher (30,000/uL if bone marrow plasma cells 50% or more) without transfusions or growth factors at screening
- Left ventricular ejection fraction 45% or higher within 8 weeks before enrollment
- Oxygen saturation above 92% without supplemental oxygen
- Negative pregnancy test for women of childbearing potential
- Agreement to use effective birth control or abstain from heterosexual activity during the study and for 6 months after last dose
You will not qualify if you...
- Prior autologous or allogeneic stem cell transplant
- Use of growth factors within 14 days of enrollment
- Platelet transfusions within 7 days of enrollment
- Current or recent use of systemic steroids or chronic immunosuppressants (except low-dose physiologic replacement)
- Active autoimmune disease requiring systemic immunosuppression
- Receiving other investigational agents or concurrent biological therapy, chemotherapy, or radiation
- Standard contraindications to myeloablative stem cell transplant
- Clinically significant or unstable arrhythmias within 2 weeks before screening
- History of optic neuritis or active central nervous system immune or inflammatory disease
- Allergic reactions to similar compounds or cetuximab
- Known bleeding disorders or hemophilia
- Stroke or intracranial hemorrhage within 6 months before screening
- History of other malignancies except certain treated cancers with no active disease for 3 years or more
- Clinically significant uncontrolled illness
- Active infection requiring antibiotics
- HIV positive
- Active viral hepatitis
- Pregnant or breastfeeding women
- Any other condition judged unsafe for participation by the investigator
- Inability to comply with study procedures or feasibility requirements
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)
Duration - Approximately 9 days
Participants receive a standard conditioning regimen, typically including carmustine, etoposide, cytarabine, and melphalan, to prepare for stem cell transplant.
Daily visits during conditioning
Duration - 1 day
Participants undergo autologous hematopoietic stem cell transplantation (autoHSCT) to replace damaged or diseased bone marrow.
1 visit (in-person) on transplant day
Duration - 8 weeks
Participants receive CMV-specific CD19-CAR T cells intravenously on day 0 and CMV-MVA triplex vaccine intramuscularly on days 28 and 56, if there is no disease progression or unacceptable toxicity.
1 infusion visit and 2 vaccination visits
Duration - Up to 15 years
Participants are followed for safety, disease progression, and survival with visits at 18-24 hours, weeks 1-3, 1 month, day 84, months 4-11, 1 year, and additional visits up to 15 years if applicable.
Multiple visits including weekly visits for first 3 weeks and monthly visits up to 1 year, then yearly visits
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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