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

• ClinicalTrials.gov Identifier: NCT03186118
• Recruitment Status: Active, not recruiting
• First Posted: June 14, 2017
• Last Update Posted: March 23, 2022
• Sponsor: Seattle Children's Hospital
• Information provided by (Responsible Party): Rebecca Gardner, Seattle Children's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
CD 19+ Acute Leukemia	Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 4, 2017
• Actual Primary Completion Date: September 13, 2021
• Estimated Study Completion Date: July 2033

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs [ Time Frame: 6 months ]
   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
2. Duration of B cell aplasia in CD19t T-APC treated patients [ Time Frame: up to 5 years ]
   MPF from peripheral blood as a measure of B cell aplasia

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Seattle Children's Hospital

Investigators

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

More Information

• Responsible Party: Rebecca Gardner, Associate Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT03186118
• Other Study ID Numbers: PLAT-03
• First Posted: June 14, 2017
• Last Update Posted: March 23, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rebecca Gardner, Seattle Children's Hospital:

pediatric; young adult; acute lymphoblastic leukemia; CD 19; leukemia; chimeric antigen receptor; T cell

Additional relevant MeSH terms:

Leukemia; Neoplasms by Histologic Type; Neoplasms