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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

ConditionsB-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
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Prior autologous/allogeneic stem cell transplant

Growth factors within 14 days of enrollment

Platelet transfusions within 7 days of enrollment

Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =< 5 mg /day, or equivalent doses of other corticosteroids) is allowed

Trial design

Design model

Single group

Treatments tested in this trial

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

    Biological/Vaccine

    Given IV

  • Autologous Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Undergo autoHSCT

  • Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

    Biological/Vaccine

    Given IM

  • Myeloablative Conditioning

    Procedure/Surgery

    Given standard conditioning regimen

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)Experimental treatment 4 interventions

Trial outcomes

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.

Time frame
Up to 15 years

Secondary outcomes

1

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

Yield of at least 10×10\^6 cytomegalovirus (CMV)-specific CD19-chimeric antigen receptor (CAR) T cells per product meeting product release requirements

Time frame
Up to 56 days
2

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

Will be assessed longitudinally. Persistence is defined as detection of \>= 0.1% of CMV-specific CD19-CAR T cells in CD3+ cells in peripheral blood, 28 days after vaccine administration, by flow cytometry and Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE) quantitative polymerase chain reaction (Q-PCR). Expansion is defined as an increase of 2-fold in CMV-specific CD19-CAR T cells after Triplex administration compared with pre-vaccination cell number. Response to Triplex will be assessed based on numbers of EGFR+, pp65-specific IFNgamma+ and CD137+T cells.

Time frame
Up to 15 years
3

Clinically significant CMV reactivation

Clinically significant defined as \> 1250 IU/ml or 500 GC/mL) CMV reactivation requiring management treatment after CAR T cell infusion as assessed by PCR.

Time frame
Up to 15 years
4

Progression-free survival (PFS)

Participants are considered a failure for this endpoint if they die (regardless of cause) or experience disease relapse.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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