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Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT02051257

Memory Enriched T Cells Following Stem Cell Transplant in Treating Patients With Recurrent B-Cell Non-Hodgkin Lymphoma

A Phase 1 study testing Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Mantle Cell Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the highest possible dose of memory enriched T cells that can be given following standard stem cell transplant before unmanageable side effects are seen in patients with B-cell non-Hodgkin lymphoma that has returned after previous treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteUnited States
Study dates
19 Jun 2014to 2 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Research participants enrolled are patients with an indication to be considered for HSCT, who are diagnosed with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) (e.g. diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], or transformed NHL), and that have either (1) recurrence/progression following prior therapy, or (2) verification of high-risk disease in first or subsequent remission
  • Karnofsky performance status (KPS) of >= 70% at time of enrollment
  • Life expectancy >= 16 weeks at time of enrollment
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate or high grade B-cell NHL (e.g., DLBCL, MCL, or transformed NHL)
  • Negative serum pregnancy test for women of child-bearing potential
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  • Research participant has an indication to be considered for autologous stem cell transplantation
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS:
  • Research participant has a released cryopreserved T cell product
  • Research participant did not have evidence of disease progression after salvage therapy and therefore underwent an autologous myeloablative transplantation with hematopoietic progenitor cell autologous (HPC[A]) rescue procedure
  • Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
  • Not requiring pressor support, not having symptomatic cardiac arrhythmias
  • Lack of acute renal failure/requirement for dialysis, as evidenced by creatinine < 1.6 mg/dL
  • Total bilirubin =< 5.0 mg/dL
  • Research participant without clinically significant encephalopathy/new focal deficits
  • No clinical evidence of uncontrolled active infectious process

Who cannot join

  • Research participants with any uncontrolled illness including ongoing or active infections; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
  • Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • Research participants with a history of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab
  • Research participants with known brain metastases (central nervous system [CNS] involvement either parenchymal or leptomeningeal involvement)
  • Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
  • Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
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  • History of allogeneic HSCT or prior autologous HSCT
  • Any standard contraindications to myeloablative HSCT per standard of care practices at COH
  • Dependence on corticosteroids
  • Defined as doses of corticosteroids of greater than or equal to 5 mg/day of prednisone or equivalent doses of other corticosteroids
  • Note: topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed
  • Currently receiving another investigational agent
  • Active autoimmune disease requiring systemic immunosuppressive therapy
  • Research participants will be excluded, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase I Study of Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate or High Grade B-Lineage Non-Hodgkin Lymphoma

This phase I trial studies the highest possible dose of memory enriched T cells that can be given following standard stem cell transplant before unmanageable side effects are seen in patients with B-cell non-Hodgkin lymphoma that has returned after previous treatment. A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Memory enriched T cells will be made from a patient's own T cells that are genetically modified in a laboratory. This means that the T cells are changed by inserting additional pieces of deoxyribonucleic acid (genetic material) into the cell to make it recognize and kill lymphoma cells. Memory enriched T cells may kill the cells that are not killed by stem cell transplant and may lower the chances of the cancer recurring.

Read the detailed description

PRIMARY OBJECTIVES: I. To assess the safety and determine the maximum tolerated dose (MTD) of each cellular immunotherapy product, cluster of differentiation (CD)19R (EQ) 28 zeta/truncated human epidermal growth factor receptor (EGFRt) + central memory T cell (Tcm) (Arm 1) and CD19R(EQ)28zeta/EGFRt+ naive memory T cell (TN/MEM) (Arm 2), in conjunction with a standard myeloablative autologous hematopoietic stem cell transplant (HSCT) for patients with high-risk intermediate or high grade B-lineage non-Hodgkin lymphomas.

SECONDARY OBJECTIVES: I. To determine the tempo, magnitude, and duration of engraftment of the transferred T cell product as it relates to the number of cells infused.

II. To study the impact of this therapeutic intervention on the development of normal CD19+ B-cell precursors in the bone marrow as a surrogate for the in vivo effector function of transferred autologous CD19R(EQ)28zeta/EGFRt+ Tcm or TN/MEM.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms. ARM 1: Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells intravenously (IV) over 10 minutes on day 2 or 3 following HSCT. ARM 2: Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT. Patients who experience disease progression and have not experienced serious treatment-related toxicities at greater than or equal to 100 days post T cell infusion will be allowed to receive an optional second T cell infusion.

After completion of study treatment, patients are followed up within 18-24 hours, then 18-72 hours, weekly for 1 month, monthly for 1 year, at 18, 24, and 36 months, and then annually thereafter for a minimum of 15 years.

Being tested
Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes, Laboratory Biomarker Analysis
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cellsBiological

    Also called CD19R:CD28:lentiviral/EGFRt+ T cells

    Given IV

  • Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytesBiological

    Also called CD19R(EQ)28zetaEGFRt+ Tn/mem Cells, CD19R(EQ)28zetaEGFRt+ Tn/Tmem

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02051257
Study groupRoleWhat they receive
Arm 1 (autologous TCM-enriched T cells)ExperimentalPatients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.
Receives: Biological: Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells; Other: Laboratory Biomarker Analysis
Arm 2 (autologous TN/MEM-enriched T cells)ExperimentalPatients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.
Receives: Biological: Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities (DLTs), defined as any grade 3 or higher toxicity, any grade 3 or greater autoimmune toxicity, or failure for a research participant with documented T cell persistence to engraft by day 21 post HSCT

    Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) and the Cytokine Release Syndrome (CRS) Clinical Symptoms \& Revised Grading System. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

    Measured: Up to 28 days

  2. Incidence of adverse events attributable to the cellular immunotherapy product

    Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

    Measured: Up to 15 years

  3. MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells based on DLTs

    Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

    Measured: 28 days

  4. MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells based on DLTs

    Toxicity and adverse events will be assessed using CTCAE v 4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

    Measured: 28 days

Secondary outcomes (2)

  1. Engraftment of the transferred T cell product

    Rates and associated 95% confidence limits will be estimated.

    Measured: Up to 28 days

  2. Levels of CD19+ B-cell precursors in the bone marrow, used as a surrogate for the in vivo effector function of transferred CD19-specific T-cells

    CD19+ B cell levels will be reported over the study period using both descriptive statistics and graphical methods for each arm.

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2014 (estimated)
  2. Study start19 Jun 2014
  3. Primary completion2 Mar 2027 (estimated)
  4. Study completion2 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
51 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02051257
Sponsor's protocol ID
13277
Other IDs
NCI-2014-00133, 13277, P50CA107399
Status last verified
Mar 2026
First submitted
29 Jan 2014
Last updated
31 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Mantle Cell Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (DLTs), defined as any grade 3 or higher toxicity, any grade 3 or greater autoimmune toxicity, or failure for a research participant with documented T cell persistence to engraft by day 21 post HSCT (time frame: Up to 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02051257.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.

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