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)

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Recruiting
participants needed

20
sponsor

University of Colorado, Denver

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Updated on 19 February 2024

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cancer

graft versus host disease

lymphoma

hodgkin's disease

flow cytometry

immunohistochemistry

systemic therapy

b-cell lymphoma

mantle cell lymphoma

follicular lymphoma

marginal zone lymphoma

diffuse large b-cell lymphoma

burkitt's lymphoma

large b-cell lymphoma

lymphoma cell count

non-hodgkin lymphoma

malt

primary mediastinal large b-cell lymphoma

Summary

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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.

Description

The objective of this Phase 1 open-label study is to assess the feasibility of UCD19 Chimeric Antigen Receptor (CAR) T Cells manufacture onsite, successful infusion of eligible subjects, and safety of UCD19 CAR T Cells infusion in subjects with relapsed/refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL).

Six (6) subjects will participate in the initial cohort of this open-label, single arm, single site study to assess dose-limiting toxicity (DLT) and safety; the first set of 3 subjects will initiate treatment with lymphodepleting chemotherapy prior to CAR T cell infusion staggered 30 days from CAR T cell dosing of the previously treated subject. Depending on the assessment of DLTs, the second set of 3 subjects may be enrolled and dosed without stagger.

After the initial 6 subjects have received treatment, an additional 14 subjects will participate in the Phase 1 expansion study.

Participants will include adults with relapsed/ primary refractory CD19 positive (i.e. CD19 expressing) B-NHL as confirmed by either flow cytometry, immunohistochemistry (IHC), or both who are not candidates for other curative forms of therapy. Enrolled participants will receive lymphodepleting chemotherapy followed by infusion of UCD19 CAR T Cells (Lentiviral Vector [LV] Transduced Autologous Peripheral Blood Lymphocytes). Participants will be enrolled up to 1 month before anticipated date of apheresis, and will be considered completed at 12 months post-treatment.

Long Term Follow Up will be conducted under a separate protocol and will occur for up to 15 Years to collect data on the long-term safety of UCD19 CAR T Cells, and for the observation, detection, and evaluation of latent adverse reactions including secondary malignancies.

While this study focuses on primary endpoints for feasibility of the manufacturing and infusion processes and safety of the administered UCD19 CAR T Cells, preliminary evidence of effectiveness will be collected and analyzed for use in planning future CAR T cell therapy studies.

Details

Condition	Lymphoma, Lymphoma
Age	18years - 80years
Treatment	UCD19 CAR T Cells
Clinical Study Identifier	NCT04240808
Sponsor	University of Colorado, Denver
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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
	No active Graft-versus-Host Disease (GvHD)
	In women of childbearing potential, willingness to use effective means of birth control for 1 year after UCD19 CAR T Cell infusion
Exclusion Criteria
	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
	Active infection that is unresponsive to antimicrobial therapy prior to lymphodepletion
	Females planning to become pregnant during the course of the study
	Unwillingness or inability to comply with study visits and study procedures for the entire duration of study participation
	Unsuitable for cellular therapy for any reason, in the opinion of the Investigator
	Any prior gene therapy, including prior CAR T cell therapy
	Active central nervous system (CNS) disease

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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)