Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Recurrence

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

B-cell Lymphoma

All Drugs and Chemicals

Vaccines

Immunologic Factors

Patients undergo leukapheresis on day -30 and receive lymphodepleting chemotherapy on days -10 to -3 per SOC on study. Patients then 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 unacceptable toxicity on study. Patients also undergo x-ray during screening and on study, as well as PET, CT, MRI, blood sample collection, and bone marrow biopsy on study and during follow-up.

Anti-CD19-CAR CMV-specific T-lymphocytes

Biospecimen Collection

Bone Marrow Biopsy

Computed Tomography

Leukapheresis

Undergo lymphodepletion chemotherapy per SOC

Lymphodepletion Therapy

Magnetic Resonance Imaging

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Positron Emission Tomography

X-Ray Imaging

Leslie L. Popplewell

Leslie L Popplewell

This phase I trial studies the safety and feasibility of cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T cells in combination with the CMV-modified vaccinia Ankara (MVA) triplex vaccine following lymphodepletion in treating patients with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refectory). 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 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 may help prevent the cancer from coming back.

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) as monotherapy and when given in combination with a multi-peptide CMV-modified vaccinia Ankara vaccine (CMV-MVA Triplex) following standard of care lymphodepletion.

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.

II. Estimate the overall and complete disease response rate at days 28 and 84 after CAR T cell infusion.

III. Determine short- and longer-term CMV-specific CD19-CAR T cell in vivo expansion and persistence.

IV. Assess whether the CMV-specific CD19-CAR T cells respond to CMV-MVA Triplex vaccine.

V. Estimate the rate of CMV reactivation after CAR T cell. VI. Estimate the one-year progression-free survival (PFS) rate and median overall survival (OS) post-CAR T cell infusion.

EXPLORATORY OBJECTIVE:

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 phased of the study (i.e., once safety of the CMV-MVA Triplex vaccine is established in the feasibility portion of the study).

OUTLINE: This is a dose-escalation study of CMV-specific CD19-CAR T cells followed by a dose-expansion study.

Patients undergo leukapheresis on day -30 and receive lymphodepleting chemotherapy on days -10 to -3 per standard of care (SOC) on study. Patients then 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 unacceptable toxicity on study. Patients also undergo x-ray during screening and on study, as well as positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), blood sample collection, and bone marrow biopsy on study and during follow-up.

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

A Pilot / Feasibility Study of Autologous CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine in Patients With Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma

Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0, and the revised American Society for Transplantation and Cellular Therapy (ASTCT) cytokine release syndrome (CRS) grading systems. 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.

Will be assessed and graded according to the NCI CTCAE v5.0, and the ASTCT consensus grading for CRS and neurotoxicity associated with immune effector cells.

Feasibility will be assessed by achieving the proposed dose of CMV-specific CD19-CAR T cells per product and meeting product release requirements for enrolled participants. The goal is to manufacture 10 x 10\^6 cells (this is a flat dose).

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 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 interferon gamma (IFNy)+ and CD137+T cells.

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.

Will be assessed according to International Working Group consensus response evaluation criteria in lymphoma 2017. The specific time trend for CMV-specific CD19-CAR T cells will be assessed using linear mixed effects modeling. The overall fit of the model will be evaluated graphically by taking a scatter plot of data for the CAR T cells and applying an overlay of the line generated by the model. To assess changes over time, functional regression modeling will be used.

Will be estimated using the product-limit method of Kaplan and Meier.

National Cancer Institute (NCI)

City of Hope Medical Center

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasm Metastasis

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Immunomodulating Agents

Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells IV on day 0. Patients with persistent CD33+ AML who are \> 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.

Anti-CD33 CAR T-cells

Karamjeet S. Sandhu

Karamjeet S Sandhu

This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient or donor'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 or donor's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.

PRIMARY OBJECTIVE:

I. Examine the anti-tumor activity and safety of administering patient-specific donor-derived (allogeneic) CD33-CAR T cells following lymphodepletion in research participants with CD33+ recurrent/refractory (r/r) acute myeloid leukemia (AML).

SECONDARY OBJECTIVE:

I. Assess activity in the form of CAR T cell expansion and persistence, to assess impact on hematopoiesis, 6-month progression free survival (PFS 6mo) rate, duration of response, and 1-year overall survival (OS) rate.

EXPLORATORY OBJECTIVES:

I. Change from baseline in numbers of CD33+ blood cells, CD33 expression on leukemia cells and hematopoietic cells.

II. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred CD33R(CD8h)BBzeta/EGFRt+ T cells.

OUTLINE: This is a dose-escalation study.

Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells intravenously (IV) on day 0. Patients with persistent CD33+ AML who are \> 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.

CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia

Phase I Study of Cellular Immunotherapy Using T Cells Lentivirally Transduced to Express a Cd33-Specific Chimeric Antigen Receptor for Patients With Cd33+ Relapsed/Refractory Acute Myeloid Leukemia

Defined as complete response (CR) or MRD- complete response with incomplete hematopoietic recovery. Rates and associated 90% Clopper and Pearson binomial confidence limits.

Rates and associated 90% toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0, and modified Cytokine Release Syndrome grading as applicable. Clopper and Pearson binomial confidence limits.

Descriptive statistics and graphical methods will be used to present expansion and persistence.

Descriptive statistics and graphical methods will be used to present T cell numbers and percentages over time.

Patients who have not had disease relapse/progression or death at the last follow-up will be censored at the time of last follow-up. Patients who never achieved CR will be excluded from the analysis. Descriptive statistics will be provided for duration of response.

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

Participants are considered a failure for this endpoint if they die, regardless of cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT05801913	High Grade B-Ce... Intermediate Gr... Recurrent B-Cel... Refractory B-Ce...	Anti-CD19-CAR C... Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Leukapheresis Lymphodepletion... Magnetic Resona... Multi-peptide C... Positron Emissi... X-Ray Imaging	18 Years -	City of Hope Medical Center
CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia	NCT05672147	Acute Myeloid L... Recurrent Adult... Refractory Acut... Secondary Acute...	Anti-CD33 CAR T... Lymphodepletion...	18 Years -	City of Hope Medical Center
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	NCT05801913	High Grade B-Ce... Intermediate Gr... Recurrent B-Cel... Refractory B-Ce...	Anti-CD19-CAR C... Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Leukapheresis Lymphodepletion... Magnetic Resona... Multi-peptide C... Positron Emissi... X-Ray Imaging	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for lymphodepletion therapy