Clinical trial NCT05757700: Study of 19(T2)28z1xx TRAC-Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: B-Cell Lymphoma
Large B-cell Lymphoma
DLBCL, Nos Genetic Subtypes
High-grade B Cell Lymphoma
Mediastinal Large B-cell Lymphoma
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2023-03-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jae Park, MD
role: PRINCIPAL_INVESTIGATOR
References: