search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
19(T2)28z1xx TRAC T cell
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-Cell Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants with Diffuse Large B-Cell Lymphoma (DLBCL) and large B cell lymphoma

Arm Description

Participants have histologically confirmed DLBCL and large B cell lymphoma. Participants will be treated with escalating doses of modified T cells.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)
The target toxicity rate for the MTD is

Secondary Outcome Measures

Full Information

First Posted
February 24, 2023
Last Updated
September 22, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Takeda
search

1. Study Identification

Unique Protocol Identification Number
NCT05757700
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 23, 2023 (Actual)
Primary Completion Date
February 23, 2025 (Anticipated)
Study Completion Date
February 23, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants with Diffuse Large B-Cell Lymphoma (DLBCL) and large B cell lymphoma
Arm Type
Experimental
Arm Description
Participants have histologically confirmed DLBCL and large B cell lymphoma. Participants will be treated with escalating doses of modified T cells.
Intervention Type
Biological
Intervention Name(s)
19(T2)28z1xx TRAC T cell
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
The target toxicity rate for the MTD is
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jae Park, MD
Phone
646-608-3743
Email
parkj6@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
M. Lia Palomba, MD
Phone
646-608-3711
Email
Palombam@MSKCC.ORG
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae Park, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jae Park, MD
Phone
646-608-3743

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

We'll reach out to this number within 24 hrs