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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Diffuse Large B Cell Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Drug: TC-110 T Cells
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>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<br>* TC-110 T Cells<br>Drug: Fludarabine<br>* Flu/Cy Lymphodepletion<br>Drug: Cyclophosphamide<br>* Flu/Cy Lymphodepletion<br>|
| Experimental: Phase 2<br>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<br>* TC-110 T Cells<br>Drug: Fludarabine<br>* Flu/Cy Lymphodepletion<br>Drug: Cyclophosphamide<br>* Flu/Cy Lymphodepletion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |