NCT05432635

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

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 (B-NHL)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. Assess the safety and describe the toxicity profile of anti-CD19-CAR CMV-specific T-lymphocytes (CMV-specific CD19-CAR T cells) alone and when given in combination with multi-peptide CMV-modified vaccinia Ankara vaccine (CMV-modified vaccinia Ankara \[MVA\] triplex vaccine) following autologous hematopoietic cell transplantation (autoHSCT) to treat participants with intermediate or high grade B-lineage non-Hodgkin lymphoma (NHL) who are in first relapse after achieving complete remission (CR) or did not achieve CR after a first line therapy. SECONDARY OBJECTIVES: I. 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 in 5 out of 6 enrolled participants. II. Determine short- and longer-term CMV-specific CD19-CAR T cell in vivo expansion and persistence. III. Assess whether the CMV-specific CD19-CAR T cells respond to CMV-MVA triplex vaccine. IV. Estimate the rate of CMV reactivation after CAR T cell infusion. V. Estimate the rate of progression-free survival (PFS) and median overall survival (OS) at 12 months post-autoHSCT. EXPLORATORY OBJECTIVES: I. 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 phase of the study (i.e., once safety of the CMV-MVA triplex vaccine is established in the feasibility portion of the study). Ia. Participants who receive CMV-specific CD19-CAR T cells in the safety lead-in portion of the study may be eligible to receive the CMV-MVA Triplex vaccine in the expansion portion of the study per principal investigator (PI) discretion and if all other criteria to proceed with vaccine administration are met. OUTLINE: 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 intravenously (IV) on day 0 and CMV-MVA triplex vaccine intramuscularly (IM) on days 28 and 56 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 18-24 hours, weeks 1-3, at 1 month, at day 84, months 4-11, and at 1 year. Patients with disease progression or starting a prohibited therapy are also followed up on months 2-4, 6, and 12 after CAR T cell infusion, and then yearly for up to 15 years.

Conditions

• B-Cell Non-Hodgkin Lymphoma
• Diffuse Large B-Cell Lymphoma
• Mantle Cell Lymphoma
• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Transformed Non-Hodgkin Lymphoma
• Transformed Non-Hodgkin Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Anti-CD19-CAR CMV-specific T-lymphocytes	Given IV
PROCEDURE	Autologous Hematopoietic Stem Cell Transplantation	Undergo autoHSCT
BIOLOGICAL	Multi-peptide CMV-Modified Vaccinia Ankara Vaccine	Given IM
PROCEDURE	Myeloablative Conditioning	Given standard conditioning regimen

Timeline

• Start date: 2023-08-01
• Primary completion: 2028-03-07
• Completion: 2028-12-30
• First posted: 2022-06-27
• Last updated: 2026-02-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study