huCART19-IL18 in CD19+ Cancers
Phase I Trial of huCART19-IL18 Cells in Patients With Relapsed or Refractory CD19+ Cancers
1 other identifier
interventional
72
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2020
CompletedFirst Posted
Study publicly available on registry
December 24, 2020
CompletedStudy Start
First participant enrolled
May 6, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2036
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2036
November 10, 2025
November 1, 2025
15 years
December 11, 2020
November 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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.
Up to 15 years post-huCART19-IL18 infusion
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.
28 days post-huCART19-IL18 infusion
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.
28 days post-huCART19-IL18 infusion
Determination of a recommended dose for expansion (RDE)
Cohorts A-C: Evaluated by Cohort/dose level using a multi-criteria decision analysis.
3 months post-huCART19-IL18 infusion
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.
3 months
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.
3 months
Secondary Outcomes (14)
Proportion of manufacturing products that meet the product release criteria
3 months
Proportion of manufactured products that meet the assigned dose
3 months
Incidence of Treatment-Emergent Adverse Events
3 months
Overall Response Rate (ORR)
3 months post-huCART19-IL18 infusion
Overall Response Rate (ORR)
1 month post-huCART19-IL18 infusion
- +9 more secondary outcomes
Study Arms (19)
Cohort A: NHL Dose Level 1a (DL1a)
EXPERIMENTAL3x10\^6 huCART19-IL18 cells administered as a single intravenous (IV) infusion or slow IV push
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.
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
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
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
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
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
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.
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
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
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
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
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.
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
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
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
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
Cohort D: NHL
EXPERIMENTAL7x10\^6 huCART19-IL18 as a single intravenous (IV) infusion or slow IV push
Cohort D: ALL
EXPERIMENTAL7x10\^6 huCART19-IL18 as a single intravenous (IV) infusion or slow IV push
Interventions
autologous Chimeric Antigen Receptor (CAR) T cells directed against the human CD19 antigen that also express human Interleukin 18 (IL-18)
Eligibility Criteria
You may qualify if:
- 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:
- a. 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
- Adequate organ function defined as:
- a. 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):
- i. 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.
- +26 more criteria
You may not qualify if:
- 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
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Pennsylvanialead
- BlueWhale Bio (Cohort D only)collaborator
Study Sites (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Related Publications (1)
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.
PMID: 40334157DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jakub Svoboda, MD
University of Pennsylvania
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2020
First Posted
December 24, 2020
Study Start
May 6, 2021
Primary Completion (Estimated)
May 1, 2036
Study Completion (Estimated)
May 1, 2036
Last Updated
November 10, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share