TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

Sponsor

TCR2 Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04323657

Collaborator

(none)

120

Enrollment

Locations

Arms

48.2

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

TC-110 T cells are a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human CD19, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex.

This is a Phase 1/2 open-label study to evaluate the safety of autologous genetically engineered TC-110 T cells in patients with aggressive NHL (DLBCL, PMBCL, TFL), high-risk indolent NHL (including MCL), or adult ALL.

Condition or Disease	Intervention/Treatment	Phase
Non Hodgkin Lymphoma Acute Lymphoblastic Leukemia Diffuse Large B Cell Lymphoma Primary Mediastinal Large B Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma	Drug: TC-110 T Cells Drug: Fludarabine Drug: Cyclophosphamide	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1/2 Trial of TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) or Acute Lymphoblastic Leukemia (ALL)

Actual Study Start Date :

Mar 27, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 The Phase 1 portion of the study will proceed according to a standard 3 + 3 dose escalation schema. Patients will be enrolled into 3 cohorts based on disease: NHL cohort, low tumor burden ALL cohort, and high tumor burden ALL cohort.	Drug: TC-110 T Cells TC-110 T Cells Drug: Fludarabine Flu/Cy Lymphodepletion Drug: Cyclophosphamide Flu/Cy Lymphodepletion
Experimental: Phase 2 The phase 2 portion of the study will evaluate the efficacy of TC-110 T cells administered at the RP2D, preceded by a lymphodepleting regimen.	Drug: TC-110 T Cells TC-110 T Cells Drug: Fludarabine Flu/Cy Lymphodepletion Drug: Cyclophosphamide Flu/Cy Lymphodepletion

Arm

Intervention/Treatment

Experimental: Phase 1

The Phase 1 portion of the study will proceed according to a standard 3 + 3 dose escalation schema. Patients will be enrolled into 3 cohorts based on disease: NHL cohort, low tumor burden ALL cohort, and high tumor burden ALL cohort.

Drug: TC-110 T Cells

TC-110 T Cells

Drug: Fludarabine

Flu/Cy Lymphodepletion

Drug: Cyclophosphamide

Flu/Cy Lymphodepletion

Experimental: Phase 2

The phase 2 portion of the study will evaluate the efficacy of TC-110 T cells administered at the RP2D, preceded by a lymphodepleting regimen.

Drug: TC-110 T Cells

TC-110 T Cells

Drug: Fludarabine

Flu/Cy Lymphodepletion

Drug: Cyclophosphamide

Flu/Cy Lymphodepletion

Outcome Measures

Primary Outcome Measures

Establish the recommended phase 2 dose (RP2D) for the NHL and ALL indications according to the observed adverse events, including potential dose-limiting toxicities (DLT). [DLTs within 28 days post-treatment]
To evaluate the efficacy of autologous genetically modified TC-110 T cells in adult patients with R/R NHL as determined by overall response rate (ORR) [ORR at 3 months for NHL patients at 3 months]
To evaluate the efficacy of autologous genetically modified TC-110 T cells in adult patients with R/R ALL as determined by overall response rate and Minimum Residual Disease (MRD) negativity rates [ORR rate and MRD negativity rate for ALL patients at 3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient is > 18 years of age at the time the Informed Consent is signed
Patient has agreed to abide by all protocol-required procedures, including study-related assessments, and management by the treating institution for the duration of the study and LTFU
Histologically confirmed NHL or ALL
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Patient must have adequate organ function as indicated by the laboratory values in the clinical protocol
Patient must be fit for leukapheresis and have adequate venous access for cell collection
Patient must have evidence of CD19 expression
Prior CD19-directed CAR T therapy is allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
3	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030