Pilot Study of Anti-CD19 Chimeric Antigen Receptor T Cells (CAR-T Cells) for the Treatment of Relapsed/Refractory CD19+ Malignancies

NCT06227026 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI143560
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, non-randomized, phase 1 study of anti-CD19 CAR-T cells against relapsed CD19 positive NHL, CLL and ALL based in a lymphodepletion regimen (fludarabine and cyclophosphamide) and using a CellReGen-based process for manufacturing CAR-T cells. This study will utilize a staggered enrollment design with a safety observation period.

Conditions

Acute Lymphoblastic Leukemia; Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Production and infusion of CAR-T therapy in 5/6 patients who have undergone successful apheresis and no more than 3/6 patients with ≥ grade 3 non-hematological CAR-T related toxicities or events of special interest within 28 days of CAR-T administration.

  To assess the feasibility of administering CAR-T cells targeting CD19 for the treatment of relapsed/refractory B cell lymphomas, relapsed/refractory chronic lymphocytic leukemia (CLL), Richter's Syndrome, or relapsed/refractory acute lymphoblastic leukemia (ALL). Feasibility is defined as production and infusion of CAR-T therapy in 5/6 patients who have undergone successful apheresis and no more than 3/6 patients with ≥ grade 3 non-hematological CAR-T related toxicities or Events of Special Interest within 28 days of CAR-T administration.

  28 days

Secondary Outcomes (3)

• Objective response rate (ORR) defined as the proportion of subjects achieving a confirmed PR or CR at Day 28 and Month 3.

  3 months

• Disease free survival at 1 year post CAR-T administration based on 2014 Lugano Criteria (NHL patients) , IWCLL criteria (CLL patients) or EWALL recommendations (ALL patients).

  1 year

• Overall survival as defined as the time from CAR-T administration until 6 months and 12 months post CAR-T administration

  12 months

Study Arms (1)

Anti-CD19 CAR-T Cell Infusion

EXPERIMENTAL

Biological: Anti-CD19 CAR-T cells

Interventions

Anti-CD19 CAR-T cells BIOLOGICAL

Anti-CD19 CAR-T cells are autologous T cells, engineered to express an extracellular single chain variable fragment (scFv) derived from a murine anti-human CD19 hybridoma clone FMC63 linked in frame to hinge region derived from human CD8, transmembrane domain derived from Tumor Necrosis Factor Receptor Super Family 19 (TNFRSF19) the transactivation costimulatory domain 4-1BB, and CD3 zeta signaling domain (Miltenyi Biotec Inc). Anti-CD19 CAR-T cells will be cryopreserved in infusible cryomedia for a later infusion. Anti-CD19 CAR-T cells will be administered in 1 to 3 bags. Bag aliquoting, cell content and cryomedia composition will be done according to specifications in the CMC.

Anti-CD19 CAR-T Cell Infusion

Eligibility Criteria

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

You may qualify if:

• Subjects aged ≥ 18 years.
• Histologically confirmed relapsed or refractory CD-19+ malignancy, including: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), Chronic Lymphocytic Leukemia (CLL)/Richter's syndrome. CD-19+ must be confirmed by immunohistochemistry or flow cytometry analysis.
• Subjects who have relapsed or refractory disease after failing at least 2 or more prior lines of therapy.
• ECOG Performance Status ≤ 2.
• Life expectancy \> 12 weeks.
• Willing to consent to 15 years of follow-up as part of IRB 110692: Long-Term Evaluation of the Biology and Outcomes of Hematopoietic Stem Cell Transplantation
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 500/mm3
• Platelet count ≥ 10,000/mm3
• Hemoglobin ≥ 8 g/dL
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN).
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
• Renal:

You may not qualify if:

• Autologous or allogeneic stem cell transplant or CAR-T therapy within 6 weeks of planned CAR-T cell infusion.
• Subjects with active infection that requires systemic treatment
• History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
• Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
• Receiving other investigational agents.
• Confirmation that washout periods listed in Appendix 10 have been followed.
• Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery.
• The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6). Patients with transformed disease are allowed.
• Known brain metastases or cranial epidural disease. Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
• QTc prolongation defined as a QTcF \> 500 ms.
• Known congenital long QT.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Sagar Patel, MD

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Kingsford

CONTACT

801-585-0115; Rachel.Kingsford@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This study will utilize a staggered enrollment design. Following the CAR-T infusion of the first subject, further enrollment will be paused for a 28 day safety observation period. If deemed safe by the Data Safety Monitoring Committee (DSMC) after this period (i.e. no stopping rules have been satisfied), enrollment of the second subject may proceed. Following the CAR-T infusion of the second subject, enrollment will again be paused for a 28 day safety observation period. Enrollment of the remaining subjects may only proceed after approval from the DSMC following the safety observation period for the second subject.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 26, 2024
• Study Start: February 20, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)