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Trial record 1 of 1 for:    NCT03186118
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Pilot Study of T-APCs Following CAR T Cell Immunotherapy for CD19+ Leukemia

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ClinicalTrials.gov Identifier: NCT03186118
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Rebecca Gardner, Seattle Children's Hospital

Tracking Information
First Submitted Date  ICMJE June 12, 2017
First Posted Date  ICMJE June 14, 2017
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE August 4, 2017
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2017)
  • 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
  • Determine the feasibility of deriving and administering a CD19t T-APC product [ Time Frame: 28 days ]
    Proportion of products successfully manufactured and infused
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2017)
  • Determine the safety of one or multiple CD19t T-APC product infusions and define the full toxicity profile of CD19t T-APC infusions [ Time Frame: up to 6 months ]
    Type, frequency, severity, and duration of adverse events will be summarized
  • Determine the feasibility of deriving and administering a CD19t T-APC product [ Time Frame: 28 days ]
    Proportion of products successfully manufactured and infused
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2019)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2017)
  • Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs [ Time Frame: 28 days ]
    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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of T-APCs Following CAR T Cell Immunotherapy for CD19+ Leukemia
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE CD 19+ Acute Leukemia
Intervention  ICMJE 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)
Study Arms  ICMJE
  • 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.
    Intervention: Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
  • 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.
    Intervention: Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
  • 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.
    Intervention: Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
  • 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.
    Intervention: Biological: T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 12, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2033
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Colleen Annesley, MD 206-987-2106 CBDCIntake@seattlechildrens.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03186118
Other Study ID Numbers  ICMJE PLAT-03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rebecca Gardner, Seattle Children's Hospital
Study Sponsor  ICMJE Seattle Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Colleen Annesley, MD Seattle Children's Hospital
PRS Account Seattle Children's Hospital
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP