Phase 1 Study of huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers

NCT07891468 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 28426 (26-8450)
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Acute Lymphoblastic Leukemia; Richter's Transformation

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety of huCART19-IL18-CD428z cells

  Type, frequency, severity, and attribution of AEs/SAEs as assessed by CTCAE V6.0

  Up to 15 years post-infusion

• Evaluate the safety of huCART19-IL18-CD428z cells

  Occurrence of treatment-limiting toxicities (TLTs)

  28 days post-huCART19-IL18-CD428z infusion

Secondary Outcomes (12)

• Evaluate manufacturing feasibility

  2 months following enrollment

• Overall Response Rate (ORR) - NHL/CLL/RT participants

  Month 3

• Overall Response Rate (ORR) - ALL participants

  Day 28

• Best Overall Response (BOR) - NHL/CLL/RT participants

  Month 3 - end of Primary Follow-Up

• Best Overall Response (BOR) - ALL participants

  Day 28 - Month 6

Study Arms (1)

Arm A

EXPERIMENTAL

Single fixed dose of 7x10\^6 huCART19-IL18-CD428z cells (Dose Level 1; DL1)

Biological: huCART19-IL18-CD428z cells

Interventions

huCART19-IL18-CD428z cells BIOLOGICAL

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.

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• b. A second confirmatory test based on one of the following methods:
• i. Antibody test from a different manufacturer or based on different principles and epitopes (Note: Combination antigen-antibody-based rapid tests may be used);
• ii. HIV-1 antigen;
• iii. Plasma HIV-1 RNA viral load;
• iv. FDA approved Western blot.
• \. Patients with one of the following B-cell malignancies:
• Non-Hodgkin's Lymphoma (NHL)- including the following sub-types:
• i. 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;

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stefan Barta, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@Pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2026
• First Posted: October 23, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 1, 2042
• Study Completion (Estimated): December 1, 2042
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)