Clinical Trials /

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

NCT03186118

Description:

This study will enroll patients who have been enrolled into study PLAT-02 and meet the entry criteria for study PLAT-03. 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.

Related Conditions:
  • Acute Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of T-APCs Following CAR T Cell Immunotherapy for CD19+ Leukemia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PLAT-03
  • NCT ID: NCT03186118

Conditions

  • CD 19+ Acute Leukemia

Interventions

DrugSynonymsArms
T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells)Cohort A

Purpose

This study will enroll patients who have been enrolled into study PLAT-02 and meet the entry criteria for study PLAT-03. 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

      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 several groups of patients we have identified: those who are predicted to lose
      persistence of their CAR T cells before Day 63, or 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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalParticipants in PLAT-02 who are eligible for, and consent to, PLAT-03 Cohort A may transition to PLAT-03 to receive their initial infusion of CAR-T cells, followed by up to 6 T-APC treatments.
  • T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
Cohort BExperimentalParticipants in PLAT-02 who are eligible for, and consent to, PLAT-03 Cohort B may transition to PLAT-03 after their initial infusion of CAR-T cells and laboratory testing on study day 14 indicates that the are at risk for early loss of CAR T cells. Up to 6 T-APC treatments will be administered to participants. If further laboratory testing prior to planned T-APC treatment indicates loss of CAR-T cells, participants may move to Cohort C.
  • T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
Cohort CExperimentalParticipants in PLAT-02 who are eligible for, and consent to, PLAT-03 Cohort C may transition to PLAT-03 after their initial infusion of CAR-T cells and laboratory testing shows early loss of CAR T cells between day 63 and day 183. Participants will receive another CAR-T cell infusion followed by up to 6 T-APC treatments.
  • T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)

Eligibility Criteria

        Inclusion Criteria:

          -  Previous treatment under protocol PLAT-02

          -  Adequate performance status

          -  Adequate renal, liver, cardiac, and respiratory function

          -  Adequate absolute lymphocyte count

          -  HIV negative; Hepatitis B and C negative within 3 months prior to enrollment.

          -  Patient has sufficient stored T cell product to manufacture appropriate doses of
             T-APCs

        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
      
Maximum Eligible Age:26 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed.
Time Frame:up to 6 months
Safety Issue:
Description:Type, frequency, severity, and duration of adverse events will be summarized

Secondary Outcome Measures

Measure:Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs
Time Frame:28 days
Safety Issue:
Description: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
Measure:Duration of B cell aplasia in CD19t T-APC treated patients
Time Frame:up to 5 years
Safety Issue:
Description:MPF from peripheral blood as a measure of B cell aplasia

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Children's Hospital

Trial Keywords

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

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