Pilot Study of T-APCs Following CAR T Cell Immunotherapy for CD19+ Leukemia

Study Overview
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Brief Summary
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Patients with relapsed or refractory CD 19+ leukemia who have achieved remission after CD19 CAR-T cell treatment sometimes relapse because the CD 19 CAR-T cells decrease in number over time. Study PLAT-03 will test whether administering T cell antigen presenting cells (T-APCs) at intervals following treatment with CAR-T cells improves CD 19 CAR-T cell persistence and reduces the incidence of leukemia relapse.

Detailed Description
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This pilot study seeks to examine the feasibility and safety of administering T cell antigen presenting cells (T-APCs) designed to reactivate and numerically expand CD19-specific CAR T cells. The underlying hypothesis to be examined is that after remission is achieved with CAR T cell treatment, the duration, magnitude, and activation state of persisting memory CAR T cells impact on the potential for durable leukemia eradication. This is of particular relevance in two groups of patients we have identified: those who are predicted to lose persistence of their CAR T cells before Day 63, and those who have definitively lost persistence of CAR T cells prior to 6 months. By providing these patients with episodic exposure to T-APCs capable of activating CD19-specific CAR T cells for proliferation and redistribution to tissue beds where tumor cells of ALL seed, ideally over several months following remission induction, it is posited that the incidence of disease relapse will be diminished.

Official Title
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Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-03: A Pilot Feasibility and Safety Study of CD19t T-Antigen Presenting Cells (T-APCs) Following CAR T Cell Immunotherapy for CD19+ Leukemia

Conditions
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CD 19+ Acute Leukemia

Intervention / Treatment
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* Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of recurrent or refractory CD19+ leukemia Adequate performance status Able to tolerate apheresis, including placement of temporary apheresis line if required Adequate renal, liver, cardiac, and respiratory function Adequate absolute lymphocyte count HIV negative; Hepatitis B and C negative within 3 months prior to enrollment. Exclusion Criteria: Evidence of active clinically significant CNS dysfunction Evidence of active malignancy other than CD19+ malignancy Evidence of active GVHD, or on immunosuppressive GVHD therapy within 4 weeks prior to enrollment

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 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: Parallel Assignment
Interventional Model Description: Subjects are assessed during the parent study for total CD 19 load in bone marrow. Participants meeting eligibility criteria are transitioned into one of 3 arms in PLAT-03.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Participants will receive CD19-targeting CAR T cells. Participants who have a total CD19 antigen load in bone marrow of <15% will be assigned to Cohort A, to receive up to 6 T-APC treatments. | Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)<br>* Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene<br>* Other names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells);|
| Experimental: Cohort B<br>Participants will receive CD19-targeting CAR T cells. Participants for whom laboratory testing on Study Day 14 indicates they are at risk for early loss of CAR T cells will be assigned to Cohort B to receive up to 6 T-APC treatments. If laboratory testing prior to planned T-APC treatment indicates loss of CAR-T cells, participants may move to Cohort C. | Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)<br>* Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene<br>* Other names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells);|
| Experimental: Cohort C<br>Participants will receive CD19-targeting CAR T cells. Participants for whom laboratory testing shows loss of CAR T cells within 6 months will be assigned to Cohort C. They will receive another CAR T cell infusion followed by up to 6 T-APC treatments. | Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)<br>* Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene<br>* Other names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells);|
| Experimental: Cohort D<br>Participants will receive CD19-targeting CAR T cells. Participants who do not meet assignment rules for Cohorts A, B, or C will be followed after CAR T cell infusion in Cohort D. | Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)<br>* Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene<br>* Other names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed. | Type, frequency, severity, and duration of adverse events will be summarized | up to 6 months | 
| Determine the feasibility of deriving and administering a CD19t T-APC product | Proportion of products successfully manufactured and infused | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs | Multiparameter Flow Cytometry (MPF) from peripheral blood as a measure of magnitude and presence of CAR T cells before and after a dose of T-APCs | 6 months | 
| Duration of B cell aplasia in CD19t T-APC treated patients | MPF from peripheral blood as a measure of B cell aplasia | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, young adult, acute lymphoblastic leukemia, CD 19, leukemia, chimeric antigen receptor, T cell