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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: CD 19+ Acute Leukemia
• Intervention / Treatment: Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; 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); Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene; Other Names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)
Experimental: Cohort B; 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); Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene; Other Names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)
Experimental: Cohort C; 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); Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene; Other Names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)
Experimental: Cohort D; 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); Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene; Other Names: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Investigators: Study Chair: Colleen Annesley, MD, Seattle Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2017
• Primary Completion (Actual): September 13, 2021
• Study Completion (Estimated): July 1, 2033

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; young adult; T cell; leukemia; acute lymphoblastic leukemia; chimeric antigen receptor; CD 19
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: PLAT-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No