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Adult Grade III Lymphomatoid GranulomatosisPhase 1NCT01815749

Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

A Phase 1 study testing autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, autologous hematopoietic stem cell transplantation and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and Cutaneous B-cell Non-Hodgkin 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 side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. 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 hematopoietic stem cell transplantation and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
8 Oct 2013to 31 May 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 grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL), and that have either recurrence/progression following prior therapy, or verification of high-risk disease in first remission
  • Karnofsky performance status of >= 70% and a 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 the history of intermediate grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL)
  • Negative serum pregnancy test for women of childbearing potential
  • Research participant has an indication to be considered for autologous stem cell transplantation
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  • All patients must have the ability to understand and the willingness to sign a written informed consent
  • ELIGIBILITY TO UNDERGO AUTOLOGOUS MYELOABLATIVE TRANSPLANTATION WITH HEMATOPOETIC PROGENITOR CELL (HPC)A RESCUE
  • Research participant meets all standard clinical parameters for candidates of autologous transplant as described in the current COH Hematopoietic Cell Transplant Standard Operating Policies, Procedures and Protocols
  • Patient Evaluation \& Selection or Deferral for hematopoietic cell transplantation (HCT)
  • Research participant is scheduled to receive a standard chemotherapy-based conditioning regimen, such as cyclophosphamide, carmustine, etoposide (CBV) or carmustine, etoposide, cytarabine, melphalan (BEAM)
  • Research participant has a cryopreserved unselected HPCA product of at least 3 x 10^6/kg CD34+ cells
  • Research participant does not have evidence of disease progression after salvage therapy
  • ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS
  • Research participant has a released cryopreserved T cell product
  • Research participant has undergone an autologous HPC(A) procedure
  • Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation of 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 - Total bilirubin =< 5.0
  • Research participant without clinically significant encephalopathy/new focal deficits
  • No clinical evidence of uncontrolled active infections process

Who cannot join

  • Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment; research participants with any signs of 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab
  • Research participants with known brain metastases (central nervous system [CNS] involvement or parenchymal or leptomeningeal involvement)
  • Research participants with presence of other malignancy or history of prior malignancy within 5 years of study entry; although patients treated with curative intent within 5 year are eligible; this exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
  • Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II 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
  • 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 Central Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma

This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect)

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and describe the full toxicity profile of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (Tcm)-enriched T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a costimulatory cluster of differentiation (CD)19-specific chimeric antigen receptors (CAR) as well as a truncated human epidermal growth factor receptor (EGFR) (CD19R:CD28 zeta/EGFR tau +Tcm) (CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplant (HSCT) for patients with high-risk intermediate grade B-lineage non-Hodgkin lymphoma (e.g., diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL] or transformed non-Hodgkin lymphoma [NHL]).

II. To determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs).

SECONDARY OBJECTIVES:

  1. 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 peripheral blood as a surrogate for the in vivo effector function of transferred autologous CD19R:CD28 zeta/EGFR tau +Tcm.

OUTLINE: This is a dose-escalation study of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells. Patients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Patients undergo myeloablative conditioning regimen per institutional standards beginning day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3 (may be delayed up to day 45 if the patient is not yet eligible). Patients who experience disease progression and have not experienced DLTs at greater than or equal to 100 days post HSCT will be allowed to receive an optional second T cell infusion.

After completion of study treatment, patients are followed up weekly for 1 month, monthly for 1 year, and then yearly for 15 years.

Being tested
autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells, autologous hematopoietic stem cell transplantation, laboratory biomarker analysis
Medical subject headings
Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular

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 CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells

    Given IV

  • autologous hematopoietic stem cell transplantationProcedure or surgery

    Undergo autologous hematopoietic stem cell transplantation

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01815749
Study groupRoleWhat they receive
Treatment (genetically modified T cell infusion)ExperimentalPatients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Patients undergo myeloablative conditioning regimen per institutional standards beginning day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3 (may be delayed up to day 45 if the patient is not yet eligible). Patients who experience disease progression and have not experienced DLTs at greater than or equal to 100 days post HSCT will be allowed to receive an optional second T cell infusion.
Receives: Biological: autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells; Procedure: autologous hematopoietic stem cell transplantation; Other: laboratory biomarker analysis

What is being measured

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

  1. Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.

    Measured: Up to 15 years

  2. MTD of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells based on dose limiting toxicities

    Graded according to the NCI CTCAE version 4.0.

    Measured: Up to day 28

Secondary outcomes (2)

  1. Engraftment of the transferred T cell products

    Rates and associated 95% confidence limits will be estimated.

    Measured: Up to 21 days

  2. CD19+ B cell precursors in the peripheral blood as a surrogate for the in vivo effector function of transferred CD19-specific T cells

    Rates and associated 95% confidence limits will be estimated.

    Measured: Up to 28 days

Timeline

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

  1. First posted21 Mar 2013 (estimated)
  2. Study start8 Oct 2013
  3. Primary completion9 Jan 2018
  4. Study completion31 May 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01815749
Sponsor's protocol ID
12224
Other IDs
NCI-2013-00590, P50CA107399
Status last verified
Jun 2026
First submitted
19 Mar 2013
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PubMed 34515338

  • Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, Norris AP, Wong CW, Urak RZ, Chang WC, Khaled SK, Siddiqi T, Budde LE, Xu J, Chang B, Gidwaney N, Thomas SH, Cooper LJ, Riddell SR, Brown CE, Jensen MC, Forman SJ. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980-90. doi: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26.

    PubMed 27118452

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 hematopoietic stem cell transplantation and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and Cutaneous B-cell Non-Hodgkin 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 21 inclusion and 11 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 25 Jun 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?

Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: Up to 15 years). The study lists 2 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 NCT01815749, which also lists 2 linked publications.

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 25 Jun 2026.

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