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Chronic Lymphocytic LeukemiaPhase 1NCT04684563

huCART19-IL18 in CD19+ Cancers

A Phase 1 study testing huCART19-IL18 in people with Chronic Lymphocytic Leukemia and Non-hodgkin Lymphoma, run by University of Pennsylvania 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
Search all trials

Trial summary

The purpose of this study is to evaluate the safety and feasibility of huCART19-IL18 cells in patients with relapsed or refractory CD19+ cancers. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
huCART19-IL18
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
1 siteUnited States
Study dates
6 May 2021to May 2036
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

  • Signed informed consent form
  • Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory
  • NHL Patients: Within 6 months of physician-investigator confirmation of eligibility as long as there has been no intervening CD19 directed therapy since expression confirmed. Results outside of this window may be used, if there is no accessible tumor site and the subject did not receive intervening CD19 directed therapy since CD19 expression was confirmed.
  • CLL and ALL Patients: At time of most recent relapse. If the subject has subsequently received CD19-directed therapy since this result was obtained, repeating testing must be performed to determine eligibility.
  • Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
  • Have no active GVHD and require no immunosuppression b. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
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  • Adequate organ function defined as:
  • Creatinine ≤ 1.6 mg/dl b. ALT/AST ≤ 3x upper limit of normal range c. Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl) d. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air e. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
  • Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility. .
  • Male or female age ≥ 18 years.
  • ECOG Performance Status that is either 0 or 1.
  • Subjects of reproductive potential must agree to use acceptable birth control methods.
  • Disease-specific criteria:
  • NHL Patients (Cohorts A and D):
  • Patients with any of the following diagnoses: Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS), germinal center or activated B-cell types;Primary Cutaneous DLBCL; Primary Mediastinal (thymic) Large B-cell Lymphoma; ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); High-grade B-cell Lymphoma, NOS; T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; or any aggressive B-cell lymphoma arising from indolent lymphoma.
  • 1. Patients must have either relapsed after, or be ineligible for, prior CAR T cell therapy, and meet one of the following criteria:
  • Relapsed/refractory disease after at least 2 prior lines of appropriate therapy; OR
  • Relapsed/refractory disease after autologous SCT; OR
  • Relapsed/refractory disease after allogeneic SCT. ii. Follicular lymphoma
  • Patients must have either relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
  • Received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy) and progressed within 2 years after second or higher line of therapy.
  • Mantle cell lymphoma
  • Patients must have either failed standard of care CAR T cell therapy (e.g., Tecartus™, etc) or other investigational CAR T cell product, OR be ineligible for standard of care Tecartus™; and
  • Patients must also meet one of the following criteria:
  • Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy; OR
  • Relapsed/refractory disease after prior autologous SCT; OR
  • Relapsed/refractory disease after prior allogeneic SCT.
  • CLL Patients (Cohort B):
  • Chronic Lymphocytic Leukemia
  • Patients with relapsed/refractory disease after at least 2 prior lines of appropriate therapy; AND
  • Patients must have previously received or be intolerant to an approved BTK inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated.
  • Large cell transformation of CLL (Richter's Transformation)
  • 1. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.
  • ALL Patients (Cohorts C and D): i. Patients with b-cell acute lymphoblastic leukemia. Note: Chronic myeloid leukemia (CML) lymphoid blast crisis is considered a sub-type of relapsed B-ALL, thus will be encompassed in our definition of B-ALL throughout; AND ii. Patients with 2nd or greater relapse or refractory disease as defined by one of the following criteria:
  • Recurrent disease in the blood or bone marrow identified morphologically, by IHC or flow; OR
  • Isolated CNS disease. Note: Patients with prior/current history of CNS3 disease will only be eligible for treatment if the CNS disease is responsive to therapy; OR
  • Recurrent extramedullary disease at other (non-CNS) sites if disease response can be assessed radiographically. Note: Patients with recurrent extramedullary disease do not need to have detectable blood or bone marrow involvement; OR
  • Any relapse after allogeneic SCT; OR
  • Patients with refractory disease as defined by one of the following:
  • Failure to achieve remission (<5% bone marrow blasts or ongoing extramedullary or CNS disease) after 2 cycles of induction chemotherapy; OR
  • Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.

Who cannot join

  • Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  • Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
  • Active acute or chronic GVHD requiring systemic therapy.
  • Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
  • RETIRED WITH PROTOCOL AMENDMENT V7
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  • Receipt of prior huCART19 therapy.
  • CNS disease as defined by disease-cohort as follows:
  • NHL/CLL Patients: Active CNS disease. Note: Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
  • ALL Patients: CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
  • Pregnant or nursing (lactating) women.
  • Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
  • Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Phase I Trial of huCART19-IL18 Cells in Patients With Relapsed or Refractory CD19+ Cancers

The purpose of this study is to evaluate the safety and feasibility of huCART19-IL18 cells in patients with relapsed or refractory CD19+ cancers.

Read the detailed description

This is a Phase I study to assess the safety, tolerability, manufacturing feasibility, pharmacokinetics, and preliminary efficacy of huCART19-IL18 cells in patients with CD19+ cancers. The study will take place in two parts: an initial Dose-Finding Phase and an Expansion Phase. In the dose-finding phase, the maximum tolerated dose will be determined using a Bayesian Optimal Interval (BOIN) design within each of the following disease-specific cohorts:

  • Cohort A: Non-Hodgkin Lymphoma (Active, Not Recruiting)
  • Cohort B: Chronic Lymphocytic Leukemia (Active, Not Recruiting)
  • Cohort C: Acute Lymphoblastic Leukemia (Active, Not Recruiting)
  • Cohort D (Expansion Phase): Non Hodgkin Lymphoma and Acute Lymphoblastic Leukemia (Active, Not Recruiting) will evaluate changes to cell activation method in the huCART19-IL18 manufacturing process using the recommended dose for expansion (RDE) arising out of the dose-finding phase.
Being tested
huCART19-IL18
Keywords
CLL, NHL, CAR-T cells
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • huCART19-IL18Biological

    autologous Chimeric Antigen Receptor (CAR) T cells directed against the human CD19 antigen that also express human Interleukin 18 (IL-18)

Study groups in NCT04684563
Study groupRoleWhat they receive
Cohort A: NHL Dose Level 1a (DL1a)Experimental3x10^6 huCART19-IL18 cells administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level -1 (DL-1)Experimental7x10^5 huCART19-IL18 cells administered as a single intravenous (IV) infusion or slow IV push; This dose level will only be explored if at least one DLT is observed at Dose Level 1a.
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level 1b (DL1b)Experimental3x10^6 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level 2 (DL2)Experimental7x10^6 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level 3 (DL3)Experimental3x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level 4 (DL4)Experimental7x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort A: NHL Dose Level 5 (DL5)Experimental3x10^8 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort B: CLL Dose Level 1b (DL1b)Experimental3x10^6 huCART19-IL18 cells administered as a single intravenous (IV) infusion or slow IV push; This dose level will only be explored if at least one DLT is observed at Dose Level 2.
Receives: Biological: huCART19-IL18
Cohort B: CLL Dose Level 2 (DL2)Experimental7x10^6 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort B: CLL Dose Level 3 (DL3)Experimental3x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort B: CLL Dose Level 4 (DL4)Experimental7x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort B: CLL Dose Level 5 (DL5)Experimental3x10^8 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort C: ALL Dose Level 1b (DL1b)Experimental3x10^6 huCART19-IL18 cells administered as a single intravenous (IV) infusion or slow IV push; This dose level will only be explored if at least one DLT is observed at Dose Level 2.
Receives: Biological: huCART19-IL18
Cohort C: ALL Dose Level 2 (DL2)Experimental7x10^6 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort C: ALL Dose Level 3 (DL3)Experimental3x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort C: ALL Dose Level 4 (DL4)Experimental7x10^7 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort C: ALL Dose Level 5 (DL5)Experimental3x10^8 huCART19-IL18 cells following lymphodepleting chemotherapy administered as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort D: NHLExperimental7x10^6 huCART19-IL18 as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18
Cohort D: ALLExperimental7x10^6 huCART19-IL18 as a single intravenous (IV) infusion or slow IV push
Receives: Biological: huCART19-IL18

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

    Cohorts A-C: Type, frequency and severity of adverse events as assessed by CTCAE V5.0. Each disease-specific cohort will be analyzed separately.

    Measured: Up to 15 years post-huCART19-IL18 infusion

  2. Occurrence of dose-limiting toxicities (DLTs)

    Cohorts A-C: Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort.

    Measured: 28 days post-huCART19-IL18 infusion

  3. Determination of Maximum Tolerated Dose (MTD)

    Cohorts A-C: Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort.

    Measured: 28 days post-huCART19-IL18 infusion

  4. Determination of a recommended dose for expansion (RDE)

    Cohorts A-C: Evaluated by Cohort/dose level using a multi-criteria decision analysis.

    Measured: 3 months post-huCART19-IL18 infusion

  5. Proportion of manufactured products that meet the product release criteria

    Cohort D: Calculated based on the proportion of subjects with huCART19-IL18 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.

    Measured: 3 months

  6. Proportion of manufactured products that meet the assigned dose

    Cohort D: Calculated based on the proportion of subjects with huCART19-IL18 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.

    Measured: 3 months

Secondary outcomes (14)

  1. Proportion of manufacturing products that meet the product release criteria

    Cohorts A-C: Calculated based on the proportion of subjects with huCART19-IL18 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted. Will be evaluated separately by each disease-specific cohort.

    Measured: 3 months

  2. Proportion of manufactured products that meet the assigned dose

    Cohorts A-C: Calculated based on the proportion of subjects with huCART19-IL18 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted. Will be evaluated separately by each disease-specific cohort.

    Measured: 3 months

  3. Incidence of Treatment-Emergent Adverse Events

    Cohort D: Type, frequency and severity of adverse events as assessed by CTCAE V5.0.

    Measured: 3 months

  4. Overall Response Rate (ORR)

    NHL and CLL Patients: The proportion of subjects with CR or PR at Month 3 as compared to baseline.

    Measured: 3 months post-huCART19-IL18 infusion

  5. Overall Response Rate (ORR)

    ALL Patients: The proportion of subjects with CR/CRi/CR(MRD-) at Day 28 as compared to baseline

    Measured: 1 month post-huCART19-IL18 infusion

  6. Best Overall Response (BOR)

    NHL and CLL Patients: The proportion of subjects with a best overall disease response of CR or PR between Month 3 and Month 12, and prior to the start of new anticancer therapy.

    Measured: 12 months post-huCART19-IL18 infusion

  7. Best Overall Response (BOR)

    ALL Patients: The proportion of subjects with CR/CRi/CR(MRD-) by Month 6, and prior to the start of new anticancer therapy.

    Measured: 6 months post-huCART19-IL18 infusion

  8. Duration of Response (DOR)

    NHL and CLL Patients: Duration from the date when CR/PR is first met at/after Month 3, to the date of relapse, death, or receipt of new anticancer therapy.

    Measured: Up to 15 years post-huCART19-IL18 infusion

  9. Duration of Remission (DOR)

    ALL Patients: Duration from the date when CR/CRi/CR(MRD-) is first met to the date of relapse, death or receipt of new anticancer therapy

    Measured: Up to 15 years post-huCART19-IL18 infusion

  10. Progression-Free Survival (PFS)

    NHL and CLL Patients: Duration of time from the huCART19-IL18 infusion to the date of the disease progression/relapse, death or receipt of new anticancer therapy

    Measured: 12 monthsUp to 15 years post-huCART19-IL18 infusion

  11. Event-Free Survival (EFS)

    ALL Patients: Duration of time from the huCART19-IL18 infusion to the date of relapse/treatment failure, death or receipt of new anticancer therapy.

    Measured: Up to 15 years post-huCART19-IL18 infusion

  12. Overall Survival (OS)

    Duration of time from the huCART19-IL18 infusion to the date of death, for any reason

    Measured: Up to 15 years post-huCART19-IL18 infusion

  13. Characterize low level disease and B cell assessment in response to huCART19-IL18 cells by Flow Cytometry

    Polychromatic flow cytometry-based assessment of leukemia and B cells, extent and duration of leukemic response

    Measured: 12 months

  14. Characterize low level disease and B cell assessment in response to huCART19-IL18 cells by Next Gen Sequencing

    Presence or absence of malignant B cells by Next-Generation Immunoglobulin heavy chain Sequencing (NGIS)

    Measured: 12 months

Timeline

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

  1. First posted24 Dec 2020
  2. Study start6 May 2021
  3. Primary completionMay 2036 (estimated)
  4. Study completionMay 2036 (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
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04684563
Sponsor's protocol ID
15420; IRB# 844955
Status last verified
Nov 2025
First submitted
11 Dec 2020
Last updated
10 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Svoboda J, Landsburg DJ, Gerson J, Nasta SD, Barta SK, Chong EA, Cook M, Frey NV, Shea J, Cervini A, Marshall A, Four M, Davis MM, Jadlowsky JK, Chew A, Pequignot E, Gonzalez V, Noll JH, Paruzzo L, Rojas-Levine J, Plesa G, Scholler J, Siegel DL, Levine BL, Porter DL, Ghassemi S, Ruella M, Rech A, Leskowitz RM, Fraietta JA, Hwang WT, Hexner E, Schuster SJ, June CH. Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure. N Engl J Med. 2025 May 8;392(18):1824-1835. doi: 10.1056/NEJMoa2408771.

    PubMed 40334157

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing huCART19-IL18 in people with Chronic Lymphocytic Leukemia and Non-hodgkin Lymphoma, run by University of Pennsylvania 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 41 inclusion and 13 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 10 Nov 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?

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 Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 (time frame: Up to 15 years post-huCART19-IL18 infusion). The study lists 6 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 NCT04684563, which also lists 1 linked publication.

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 10 Nov 2025.

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huCART19-IL18 in CD19+ Cancers (NCT04684563) | AzTrials