Non-Hodgkin LymphomaPhase 1NCT07891468
Phase 1 Study of huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers
A Phase 1 study testing huCART19-IL18-CD428z cells in people with Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia, run by University of Pennsylvania at 1 site in United States.
Trial summary
This research study is being conducted to evaluate an experimental drug called huCART19-IL18-CD428z cells in patients living with HIV who have been diagnosed with Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Acute Lymphoblastic Leukemia (ALL), and Richter's Transformation (RT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia
- What is being tested?
- huCART19-IL18-CD428z cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Dec 2042
- Phase
- Phase 1
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
- Male or female age ≥ 18 years.
- HIV-1 infection diagnosed in accordance with WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines. This requires confirmation of the initial test result using a different qualified method from the initial assessment as follows:
- Any FDA approved rapid HIV test or HIV enzyme/chemiluminescence immunoassay (E/CIA);
- AND
- A second confirmatory test based on one of the following methods:
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- Antibody test from a different manufacturer or based on different principles and epitopes (Note: Combination antigen-antibody-based rapid tests may be used);
- OR
- HIV-1 antigen;
- OR
- Plasma HIV-1 RNA viral load;
- OR
- FDA approved Western blot.
- 4. Patients with one of the following B-cell malignancies:
- Non-Hodgkin's Lymphoma (NHL)- including the following sub-types:
- Patients with any of the following large B-cell lymphoma diagnoses who are relapsed/refractory after at least 2 prior lines of appropriate therapy:
- Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS);
- 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;
- Any aggressive B-cell lymphoma arising from indolent lymphoma.
- Follicular Lymphoma (FL)- relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy).
- Mantle Cell Lymphoma- relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Single agent monoclonal antibody therapy does not count towards prior lines of therapy.
- Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Single agent monoclonal antibody therapy does not count towards prior lines of therapy.
- Chronic Lymphocytic Leukemia (CLL):
- 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.
- Richter's Transformation (RT; Large cell transformation of CLL)- Patients must be primary refractory or have received at least 1 prior line of treatment for Richter's Transformation.
- Acute Lymphoblastic Leukemia (ALL)- patients with 2nd or greater relapsed 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:
- 1. Failure to achieve remission (<5% bone marrow blasts or ongoing extramedullary or CNS disease) after 2 cycles of induction chemotherapy;
- OR
- 2. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.
- 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
- 5. 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/RT/ALL Patients: At time of most recent relapse. If the subject has subsequently received CD19-directed therapy since this result was obtained, repeat testing must be performed to determine eligibility.
- 6. Clinically stable on an antiretroviral therapy (ART) regimen, without changes within the 28 days prior to eligibility confirmation by a physician-investigator. No changes to the current ART regimen planned as confirmed by the participant's primary infectious disease physician.
- 7. Viral Load ≤ 30 copies/mL by Hologic's Aptima® HIV-1 Quant Dx Assay within 30 days prior to physician-investigator confirmation of eligibility
- 8. ECOG Performance Status that is either 0 or 1.
- 9. Adequate organ function defined as:
- Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis
- ALT/AST ≤ 3x upper limit of normal
- Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl.
- Left Ventricle Ejection Fraction (LVEF) ≥40% confirmed by ECHO
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
- 10. Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility.
- 11. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
- Have no active GVHD and require no immunosuppression
- Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
Who cannot join
- Active hepatitis B or active hepatitis C infection.
- Any 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.
- Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- Active acute or chronic GVHD requiring systemic therapy.
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- Dependence on systemic steroids or immunosuppressant medications.
- Receipt of prior huCART19-IL18 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.
- 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.
- Current antiretroviral therapy (ART) regimen includes a non-nucleoside reverse transcriptase inhibitor (NNRTI).
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Abramson Cancer Center Clinical Trials Service contact
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Abramson Cancer Center Clinical Trials Service, 215-349-8245, PMCancerResearch@pennmedicine.upenn.edu
About this study
This research study is being conducted to evaluate an experimental drug called huCART19-IL18-CD428z cells in patients living with HIV who have been diagnosed with Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Acute Lymphoblastic Leukemia (ALL), and Richter's Transformation (RT).
Read the detailed description
This is a phase 1, open-label study to assess the safety, feasibility, and preliminary efficacy of huCART19-IL18-CD428z cells in patients with HIV that have CD19 positive cancers. huCART19-IL18-CD428z cells are genetically modified autologous T cells engineered by co-transduction with two lentiviral vectors: a). huCART19-IL18 targeting the CD19+ B-cells and b). C34-CD4CAR_CD28 targeting HIV. This investigational product is primarily intended to treat the patient's CD19-positive cancer. However, by co-expressing CD19-targeting and HIV-specific CARs in the same T cell, we aim to use cancer cells to stimulate T-cell growth, which may also help HIV-specific CAR T cells multiply and survive longer in the body.
This study will be initiated as a single arm study (Treatment Arm A), which will evaluate a single fixed dose of huCART19-IL18-CD428z cells following lymphodepleting chemotherapy. In participants who have a complete response to the huCART19-IL18-CD428z cells, an optional analytical treatment interruption (ATI) may be performed to evaluate the effectiveness of the CAR T cells to delay or prevent viral rebound in the absence of antiretroviral therapy.
- Conditions
- Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia, Richter's Transformation
- Being tested
- huCART19-IL18-CD428z cells
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, 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-IL18-CD428z cellsBiological
huCART19-IL18-CD428z cells are genetically modified autologous T cells engineered by co-transduction with two lentiviral vectors: a). huCART19-IL18 targeting the CD19+ B-cells and b). C34-CD4CAR_CD28 targeting HIV.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Single fixed dose of 7x10^6 huCART19-IL18-CD428z cells (Dose Level 1; DL1) Receives: Biological: huCART19-IL18-CD428z cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety of huCART19-IL18-CD428z cells
Type, frequency, severity, and attribution of AEs/SAEs as assessed by CTCAE V6.0
Measured: Up to 15 years post-infusion
Evaluate the safety of huCART19-IL18-CD428z cells
Occurrence of treatment-limiting toxicities (TLTs)
Measured: 28 days post-huCART19-IL18-CD428z infusion
Secondary outcomes (12)
Evaluate manufacturing feasibility
Occurrence of product release failures; occurrence of dose failures
Measured: 2 months following enrollment
Overall Response Rate (ORR) - NHL/CLL/RT participants
Proportion of subjects with CR or PR at Month 3 as compared to baseline
Measured: Month 3
Overall Response Rate (ORR) - ALL participants
Proportion of subjects with CR/CRi/CRh/CRMRD- at Day 28 as compared to baseline.
Measured: Day 28
Best Overall Response (BOR) - NHL/CLL/RT participants
Proportion of subjects with a best overall response of CR or PR recorded between Month 3 and the end of Primary Follow-Up, as compared to baseline.
Measured: Month 3 - end of Primary Follow-Up
Best Overall Response (BOR) - ALL participants
Proportion of subjects with a best overall response of CR/CRi/CRh/CRmrd- between Day 28 and Month 6, as compared to baseline.
Measured: Day 28 - Month 6
Duration of Response (DOR) - NHL/CLL/RT participants
Time from the date when the response criteria of CR/PR is first met (at or following Month 3), to the date of disease progression/relapse or death, whichever occurs first.
Measured: Up to 15 years post-huCART19-IL18-CD428z infusion
Duration of Response (DOR) - ALL participants
Time from the date when the response criteria of CR/CRi/CRh/CRmrd- is first met (at or following Day 28), to the date of disease progression/relapse or death, whichever occurs first.
Measured: Up to 15 years post-huCART19-IL18-CD428z infusion
Progression-free Survival (PFS) - NHL/CLL/RT participants
Duration of time from the huCART19-IL18-CD428z infusion to the date of confirmed disease progression or death, whichever occurs first.
Measured: Up to 15 years post-huCART19-IL18-CD428z infusion
Event-free Survival (EFS) - ALL participants
Duration of time from the initial huCART19-IL18-CD428z infusion to the earliest date of disease progression/relapse, receipt of new anticancer therapy (including huCART19-IL18-CD428z retreatment and/or HSCT, even if in the setting of ongoing CR), or death
Measured: Up to 15 years post-huCART19-IL18-CD428z infusion
Overall Survival (OS)
Duration of time from the first huCART19-IL18-CD428z infusion to the date of death
Measured: Up to 15 years post-huCART19-IL18-CD428z infusion
Evaluate the effectiveness of huCART19-IL19-CD428z cells to delay or prevent viral rebound in the absence of antiretroviral therapy
HIV viral rebound using Hologic's Aptima® HIV-1 Quant Dx Assay
Measured: Up to 2 years post-huCART19-IL18-CD428z infusion and in the setting of the analytical treatment interruption (ATI), if performed.
Evaluate the effectiveness of huCART19-IL19-CD428z cells to delay or prevent viral rebound in the absence of antiretroviral therapy
Duration of Analytical Treatment Interruption (ATI)
Measured: Up to 2 years post-huCART19-IL18-CD428z infusion and in the setting of the analytical treatment interruption (ATI), if performed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2026
- Study startJan 2027 (estimated)
- Primary completionDec 2042 (estimated)
- Study completionDec 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefan Barta, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07891468
- Sponsor's protocol ID
- 28426 (26-8450)
- Status last verified
- Oct 2026
- First submitted
- 16 Oct 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No