19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04464200

Collaborator

Takeda (Industry)

Enrollment

Location

Arm

47.8

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of 19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find this dose, they can test it in future participants to see if it is effective in treating their relapsed/refractory B-cell cell cancers. This study will also look at whether 19(T2)28z1xx CAR T cells work against participants' cancer.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma Primary Mediastinal Large B Cell Lymphoma Transformed Follicular Lymphoma to Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Indolent Non-Hodgkin Lymphoma Marginal Zone Lymphoma Waldenstrom Macroglobulinemia Burkitt's Lymphoma Primary CNS Lymphoma	Drug: 19(T2)28z1xx CAR T cells	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a standard phase I open-label dose-escalation trial. Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the MTD. There are 4 planned dose levels with one additional de-escalation dose level. A 3+3 design will be used to establish the RP2D. Once the RP2D is determined, the study will open to Dose Expansion phase and up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase).This is a standard phase I open-label dose-escalation trial. Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the MTD. There are 4 planned dose levels with one additional de-escalation dose level. A 3+3 design will be used to establish the RP2D. Once the RP2D is determined, the study will open to Dose Expansion phase and up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of CD19-Targeted 19(T2)28z1xx Chimeric Antigen Receptor (CAR) Modified T Cells in Adult Patients With Relapsed or Refractory B-cell Malignancies

Actual Study Start Date :

Jul 6, 2020

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 19(T2)28z1xx CAR T cells Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6 and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.	Drug: 19(T2)28z1xx CAR T cells 2-7 days following the completion of the conditioning chemotherapy, patients will receive the CAR- T cells by IV infusion over 1-3 days depending on the dose level and formulation of the final CAR- T cells.

Arm

Intervention/Treatment

Experimental: 19(T2)28z1xx CAR T cells

Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6 and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.

Drug: 19(T2)28z1xx CAR T cells

2-7 days following the completion of the conditioning chemotherapy, patients will receive the CAR- T cells by IV infusion over 1-3 days depending on the dose level and formulation of the final CAR- T cells.

Outcome Measures

Primary Outcome Measures

Recommended Phase II Dose (RP2D) [28 days post infusion]
Dose escalation will use a 3+3 design. DLT-evaluable participants are defined as those participants who were infused with 19(T2)28z1XX CAR T cells and who were monitored for toxicities during the first 28 days of post infusion.

Secondary Outcome Measures

overall response rate (ORR) [2 years]
Response and progression of the disease will be evaluated in this study using the Lugano Classification

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years of age
Creatinine ≤2.0 mg/100 ml, 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 6 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.
Patients with active CNS disease
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.
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 CD19 CAR T cells 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.