Study of Feasibility and Safety of UCD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Subjects With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (B-NHL)

NCT04240808 | Completed Phase 1 FDA Drug

• 1 other identifier: 19-2807
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether immune cells modified to recognize B-cell non-Hodgkin lymphoma (NHL) can be successfully manufactured at the University of Colorado Anschutz and whether these cells can be administered with an acceptable safety profile. Adults who have been diagnosed with B-cell non-Hodgkin lymphoma (NHL) that has relapsed or no longer responds to chemotherapy (relapsed or refractory) may be eligible to participate in this study. The investigators will use participants own immune cells, called T cells, to kill the lymphoma. These T cells are involved in fighting infections and in some cases, can also kill cancer cells. The investigators will extract T cells from the participant's blood, modify the cells in a laboratory, and then return teh cells to the participant's body via intravenous (IV) injection. In the laboratory, the investigators will add a new gene into the T cells that allows the T cells to recognize and kill the lymphoma cells, and allows these modified cells to multiply and increase in numbers. To put the new gene into your T cells, the investigators will use a weakened virus. The virus is modified so that it cannot multiply or spread once the cells are infused.

Conditions

Non Hodgkin Lymphoma

Keywords

Car T; Car T Cells; Cancer; B-Cell Non-Hodgkin's Lymphoma; B-NHL

Outcome Measures

Primary Outcomes (4)

• Feasibility: Successful manufacture of UCD19 CAR T Cells, as determined by the number of successfully manufactured doses

  The successful manufacture of UCD19 Chimeric Antigen Receptor (CAR) T Cells onsite meeting the IND-defined release criteria. Manufacture of UCD19 CAR T Cells will begin after enrollment and be completed within 1 month. Success will be determined by whether or not the participant's CAR T Cell count meets the target dose required for infusion at Day 0. The number of successfully manufactured doses will be reported.

  Day 0 (infusion)

• Feasibility: Percent of Participants successfully infused with UCD19 CAR T Cells

  The percent of participants who are able to receive an infusion of UCD19 CAR T cells.

  Day 0 (infusion)

• Safety: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) within 30 days after treatment

  The number of subjects who receive UCD19 CAR T Cells and experience a DLT within 30 days after treatment, as defined herein using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Up to 30 Days Post-Infusion

• Safety: Percent of Participants Who Experience a Dose Limiting Toxicity (DLT) within 30 days after treatment

  The percent of all subjects who receive UCD19 CAR T Cells and experience a DLT within 30 days after treatment, as defined herein using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Up to 30 Days Post-Infusion

Secondary Outcomes (8)

• Efficacy: Overall response rate (Complete Response (CR)/Partial Response (PR)/Stable Disease (SD)) at 90 days

  90 Days Post-Infusion

• Efficacy: Overall response rate (Complete Response (CR)/Partial Response (PR)/Stable Disease (SD)) at 6 Months

  6 Months Post-Infusion

• Efficacy: Overall response rate (Complete Response (CR)/Partial Response (PR)/Stable Disease (SD)) at 1 Year

  1 Year Post-Infusion

• Efficacy: Rate of participants with Complete Response at 6 Months

  6 Months Post-Infusion

• Efficacy: Rate of participants with Complete Response at 1 Year

  1 Year Post-Infusion

Study Arms (1)

UCD19 CAR T Cells

EXPERIMENTAL

Participants will receive lymphodepleting chemotherapy followed by infusion of UCD19 CAR T Cells (Lentiviral Vector \[LV\] Transduced Autologous Peripheral Blood Lymphocytes

Biological: UCD19 CAR T Cells

Interventions

UCD19 CAR T Cells BIOLOGICAL

Lymphodepleting chemotherapy followed by infusion of UCD19 CAR T Cells (Lentiviral Vector \[LV\] Transduced Autologous Peripheral Blood Lymphocytes)

UCD19 CAR T Cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated Informed Consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the parent study and the long-term follow-up observational study.
• Male or non-pregnant, non-lactating females, aged 18 to 80 years.
• Performance status according to the Eastern Cooperative Oncology Group ≤ 2.
• Failed two or more lines of systemic therapy.
• Unable to receive commercially available CD19 CAR T Cells.
• Relapsed or primary refractory CD19 positive (i.e. CD19 expressing) B-NHL of the following types as confirmed by either flow cytometry, Immunohistochemistry (IHC), or both:
• Diffuse large B-cell lymphoma (DLBCL)
• Burkitt lymphoma
• Intermediate lymphoma between Burkitt and DLBCL
• Primary Mediastinal B-cell lymphoma (PMBL)
• Follicular lymphoma
• Mantle cell lymphoma (MCL)
• Marginal zone lymphoma (MZL)
• No available curative alternative treatment, as determined by primary treating oncologist.

You may not qualify if:

• Prior therapies:
• Received monoclonal antibody therapy within 14 days of the apheresis; or
• Received immunomodulatory drugs (lenalidomide, tyrosine kinase inhibitors) within 14 days of the apheresis; or
• Received corticosteroids more than 7.5mg/day within 14 days of the apheresis (physiologic replacement allowed up until apheresis, as clinically indicated); or
• Allogeneic hematopoietic stem cell transplant with 90 days (immunosuppressive therapy for at least 4 weeks) of apheresis; or
• Donor lymphocyte infusion within 4 weeks of apheresis.
• Cluster of differentiation 3 (CD3) count \<0.15 x 106 cells/mL
• Severe psychiatric illness that could impede the patient's ability to provide informed consent and/or adhere to the parent protocol and/or the long-term follow-up protocol.
• Active HIV (Acquired Immune Deficiency Syndrome) or history of HIV infection, as directed by schedule or if known.
• Active Hepatitis B or Hepatitis C infection.
• Diffusion capacity of the lungs for carbon monoxide \< 40% predicted prior to lymphodepletion.
• Left ventricular ejection fraction \< 40% (evaluated by echocardiogram \[ECHO\] or Multigated Acquisition Scan \[MUGA\]) prior to lymphodepletion.
• Transaminases \> 5x upper limit of normal prior to lymphodepletion.
• Serum Bilirubin \> 4 mg/dL prior to lymphodepletion.
• Serum Creatinine \> 1.6 mg/dL or measured creatinine clearance \< 50 mL/min prior to lymphodepletion.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Neoplasms; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michael Verneris, MD

  University of Colorado Denver, Anschutz Medical Campus

  STUDY DIRECTOR

• Manali Kamdar, MD

  University of Colorado Denver, Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

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: January 22, 2020
• First Posted: January 27, 2020
• Study Start: July 17, 2020
• Primary Completion: March 24, 2023
• Study Completion: October 23, 2023
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)