Study of 19(T2)28z1xx TRAC-Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this research is to evaluate if study therapy, 19(T2)28z1xx TRAC-chimeric antigen receptor (CAR) T cells, may be an effective treatment for people with relapsed/refractory B-cell lymphoma. Researchers will also evaluate if this study therapy is safe, and to look for the highest dose that causes few or mild side effects in participants.

Official Title
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A Phase I Study of T-cell Receptor Alpha Constant (TRAC) Locus Integrated CD19-Targeted 19(T2)28z1xx Chimeric Antigen Receptor (CAR) Modified T Cells in Adult Patients With CD19+ Relapsed or Refractory Large B-Cell Lymphoma

Conditions
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B-Cell Lymphoma, Large B-cell Lymphoma, DLBCL, Nos Genetic Subtypes, High-grade B Cell Lymphoma, Mediastinal Large B-cell Lymphoma

Intervention / Treatment
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* Biological: 19(T2)28z1xx TRAC T cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age Creatinine ≤1.5 mg/100 ml or creatinine clearance ≥ 45ml/min/m2 , direct bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x upper limit of normal (ULN) Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry. Histologically confirmed DLBCL and large B cell lymphoma, including DLBCL, not otherwise specified (NOS), or Transformed DLBCL from follicular lymphoma, or High-grade B cell lymphoma (excluding Burkitt's lymphoma), or Primary mediastinal large B cell lymphoma AND Chemotherapy refractory disease, defined as a failure to achieve at least a partial response or disease progression within 12 months to the last therapy, OR Disease progression or recurrence in ≤12 months of prior autologous stem cell transplant (ASCT), OR Relapsed disease after 2 or more prior chemoimmunotherapies with at least one containing an anthracycline and CD20 directed therapy Patients need to have radiographically documented disease Exclusion Criteria: ECOG performance status ≥2. Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished. Active CNS disease Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan. Patients with the following cardiac conditions will be excluded: New York Heart Association (NYHA) stage III or IV congestive heart failure Myocardial infarction ≤6 months prior to enrollment History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration ≤6 months prior to enrollment Patients with HIV or active hepatitis B or hepatitis C infection are ineligible. Patients with prior allogeneic hematopoietic stem cell transplant are eligible, if more than 3 months from transplant and if patients have no active graft versus host disease (GvHD) and not on systemic immunosuppressive therapy. Prior CD19-directed therapy including commercially approved or investigational CD19 CAR T cells or BiTEs is allowed, as long as expression of CD19 is confirmed by flow cytometry or immunohistochemistry. Patients with uncontrolled systemic fungal, bacterial, viral or other infection are ineligible. Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin. Patients with presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible. Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Diffuse Large B-Cell Lymphoma (DLBCL) and large B cell lymphoma<br>Participants have histologically confirmed DLBCL and large B cell lymphoma. Participants will be treated with escalating doses of modified T cells. | Biological: 19(T2)28z1xx TRAC T cell<br>* Participants will be treated with escalating doses of modified T cells. Dose level -1: 3 x 10^6 Dose level 1: 10 x 10^6 Dose level 2: 30 x 10^6 Dose level 3: 100 x 10^6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | The target toxicity rate for the MTD is | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-Cell Lymphoma, Large B-cell Lymphoma, DLBCL, High-grade B cell lymphoma, Mediastinal Large B-cell Lymphoma, TRAC-CAR T cells, Memorial Sloan Kettering Cancer Center, 22-401