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

B-Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05757700
• Other study ID #: 22-401
• Status: Recruiting
• Phase: Phase 1
• Start date: February 23, 2023
• Est. completion date: February 23, 2025

Study information

• Verified date: February 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Jae Park, MD
• Phone: 646-608-3743
• Email: parkj6[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: February 23, 2025
• Est. primary completion date: February 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-Cell Lymphoma
• DLBCL, Nos Genetic Subtypes
• Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Mediastinal Large B-cell Lymphoma

Intervention

Biological:
• 19(T2)28z1xx TRAC T cell
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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	The target toxicity rate for the MTD is	up to 1 year

External Links

•   Memorial Sloan Kettering Cancer Center