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Recurrent Chronic Lymphocytic LeukemiaPhase 1NCT06343376

Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies

A Phase 1 study testing Biopsy, Biospecimen Collection and Bone Marrow Aspiration in people with Recurrent Chronic Lymphocytic Leukemia and Recurrent Diffuse Large B-Cell Lymphoma, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells called EGFRt/19-28z/IL-12 CAR T cells, and to see how they work in treating patients with hematologic malignancies that makes a protein called CD19 (CD19-positive) that has come back after a period of improvement… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
26 Nov 2024to 3 Jan 2025
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Patients with relapsed refractory B Cell malignancies which commonly express CD-19.
  • Eligible disease subtypes include the following:
  • Patients with diffuse large B-cell lymphoma (de novo or diffuse large B-cell lymphoma [DLBCL] transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia) or high grade B-cell Lymphoma (HGBL):
  • Relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following 2 or more prior chemoimmunotherapy regimens containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring further treatment.
  • Relapse following a single prior chemoimmunotherapy regimen containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and considered ineligible for high dose chemotherapy and autologous stem cell rescue as determined by the investigator.
  • Patients must have at least one fludeoxyglucose F-18 (FDG)-avid (PET-avid) measurable lesion.
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  • Biopsy confirmation of relapsed or refractory DLBCL is required.
  • Chronic lymphocytic leukemia after 2 lines of therapy including a BTKi (bruton tyrosine kinase inhibitor).
  • Mantle cell lymphoma after 2 lines of therapy. Patients must have previously received chemoimmunotherapy and a prior BTK inhibitor.
  • Follicular lymphoma after 2 lines of therapy.
  • For cohort 1A specifically, patients must additionally have received a prior CD19-targeted CAR T-cell therapy or not have an indication for a Food and Drug Administration (FDA)-approved commercial CD19-targeted CAR T-cell therapy. This will include patients with relapsed/refractory DLBCL, FL, CLL and MCL.
  • For cohorts other than cohort 1A (and if needed, cohort -1), patients with an indication for an FDA approved commercial CD19-targeted CAR T-cell therapy are eligible following an informed consent discussion that reviews the risks and benefits of the FDA-approved commercial CD19-targeted CAR T-cell therapy vs the investigational product.
  • Prior CD19-targeted therapies, including CAR T-cell therapy, does not exclude participation; however, CD19 expression by immunohistochemical staining or flow cytometry must be confirmed prior to enrollment for patients who have received such therapies.
  • Age ≥ 18 years of age.
  • Creatinine Clearance > 30 mL/min (Cockroft-Gault equation).
  • Direct bilirubin ≤ 2.0 mg/dL (unless related to disease).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (unless related to disease).
  • Adequate pulmonary function as assessed by ≥ 90% oxygen saturation on room air by pulse oximetry.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Patients of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

Who cannot join

  • Pregnant or lactating patients.
  • Impaired cardiac function (left ventricular ejection fraction [LVEF] < 40%) as assessed by ECHO or MUGA scan during screening.
  • Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T cell suppressive therapy are ineligible.
  • Patients with active autoimmune disease requiring systemic T cell suppressive therapy are ineligible.
  • Patients with following cardiac conditions will be excluded:
  • New York Heart Association (NYHA) stage III or IV congestive heart failure.
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  • Myocardial infarction ≤ 6 months prior to enrollment.
  • Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
  • Patients with HIV are ineligible.
  • Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus deoxyribonucleic acid [DNA] by polymerase chain reaction [PCR] and/or positivity for hepatitis B surface antigen) are ineligible.
  • Patients with active hepatitis C infection (as manifest by detectable hepatitis C virus ribonucleic acid [RNA] by PCR) are ineligible. Patients with detectable antibodies to hepatitis C virus will be screened by PCR for evidence of active infection.
  • Patients with uncontrolled systemic fungal, bacterial, viral or other infection are ineligible.
  • Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.
  • Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.
  • Patients with primary central nervous system (CNS) disease are ineligible.
  • Unwilling or unable to follow protocol requirements.
  • Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I Trial of CD19-Targeted Chimeric Antigen Receptor (CAR) Modified T Cells Genetically Engineered to Secrete Interleukin 12 (IL-12) and With a Truncated Human Epidermal Growth Factor Receptor (EGFRt) in Patients With Relapsed or Refractory CD19+ Hematologic Malignancies

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells called EGFRt/19-28z/IL-12 CAR T cells, and to see how they work in treating patients with hematologic malignancies that makes a protein called CD19 (CD19-positive) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Chimeric Antigen Receptor (CAR) T-cell Therapy is 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 to the T cells 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 for treatment of certain cancers. To improve the effectiveness of the modified T cells and to help the immune system fight cancer cells better, the modified T cells given in this study will include a gene that makes the T cells produce a cytokine (a molecule involved in signaling within the immune system) called interleukin-12 (IL-12). The researchers think that IL-12 may improve the effectiveness of the modified T cells, and it may also strengthen the immune system to fight cancer. Giving EGFRt/19-28z/IL-12 CAR T cells may be safe and tolerable in treating patients with relapsed or refractory CD19+ hematologic malignancies.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety, toxicity and maximum tolerated dose (MTD) of EGFRt/19-28z/IL-12 CAR T-lymphocytes (EGFRt/19-28z/IL-12 CAR T cells) in patients with relapsed or refractory CD19+ aggressive hematologic malignancies.

SECONDARY OBJECTIVES:

  1. To assess the anti-tumor efficacy of adoptively transferred EGFRt/19-28z/IL-12 T cells.

II. To assess the in vivo persistence of adoptively transferred EGFRt/19-28z/IL-12 T cells.

EXPLORATORY OBJECTIVES:

  1. To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

II. To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

III. To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

IV. To determine the proportion of evaluable patients who achieve minimal residual disease (MRD)-negativity in peripheral blood and/or bone marrow.

  1. To assess phenotype and in vitro function of end-of-production (EOP) EGFRt/19-28z/IL-12 CAR T cells and phenotype at recovery following CAR T cell administration.

OUTLINE: This is a dose-escalation study of EGFRt/19- 28z/IL-12 CAR T cells. Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells intravenously (IV) over 5 to 30 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET) as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

COHORT B: Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

After completion of study treatment, patients are followed up weekly for 4 weeks, every 4 weeks until 24 months, every 3 months thereafter for 1 year, then annually for up to 5 years, followed by long-term follow up for up to 15 years.

Being tested
Biopsy, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518

    Given IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • EGFRt/19-28z/IL-12 CAR T-lymphocytesBiological

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET

Study groups in NCT06343376
Study groupRoleWhat they receive
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)ExperimentalPatients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: EGFRt/19-28z/IL-12 CAR T-lymphocytes; Procedure: Leukapheresis; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)ExperimentalPatients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Biological: EGFRt/19-28z/IL-12 CAR T-lymphocytes; Drug: Fludarabine Phosphate; Procedure: Leukapheresis; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

What is being measured

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

  1. Incidence of adverse events

    Will be graded on a scale of 1 to 5 as described by the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).

    Measured: Up to 5 years

  2. Maximal tolerated dose (MTD) of EGFRt/19-28z/IL-12 chimeric antigen receptor T-cells

    Will be defined as the highest dose with an observed incidence of dose limiting toxicities in no more than one out of six patients treated at a particular dose level. Will be assessed using NCI CTCAE v 5.0.

    Measured: Within 30 days from the final infusion of the EGFRt/19-28z/IL-12 T cells

Secondary outcomes (6)

  1. Incidence of complete remission (CR)/complete remission with incomplete count recovery (CRi)

    Measured: Within 3 months of CAR T-cell infusion

  2. Incidence of CR/CRi + partial response (PR) (ORR)

    Measured: Within 3 months of CAR T-cell infusion

  3. Event free survival

    Will be computed using the Kaplan- Meier method.

    Measured: Up to 5 years

  4. Overall survival

    Will be computed using the Kaplan- Meier method.

    Measured: Up to 5 years

  5. Progression-free survival

    Measured: Up to 5 years

  6. Modified T-cell persistence

    Will be determined by the presence of detectable CAR T-cells (quantitative polymerase chain reaction or multiparameter flow cytometry).

    Measured: Up to 5 years

Timeline

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

  1. First posted2 Apr 2024
  2. Study start26 Nov 2024
  3. Primary completion3 Jan 2025
  4. Study completion3 Jan 2025

Why it stopped: Manufacturing issues

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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06343376
Sponsor's protocol ID
I-3641523
Other IDs
NCI-2024-01818, I-3641523
Status last verified
Jul 2025
First submitted
25 Mar 2024
Last updated
3 Aug 2025
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 Biopsy, Biospecimen Collection and Bone Marrow Aspiration in people with Recurrent Chronic Lymphocytic Leukemia and Recurrent Diffuse Large B-Cell Lymphoma, run by Roswell Park Cancer Institute 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 17 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: stopped early, as of the sponsor's last update on 3 Aug 2025. 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?

The study was stopped early (reason given: Manufacturing issues). Results are not available in the source record.

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 adverse events (time frame: Up to 5 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 NCT06343376.

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 3 Aug 2025.

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