Description:
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.
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
Interventions
Drug | Synonyms | Arms |
---|
T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC) | CD19+ Chimeric Antigen Receptor T-cells (CAR-T cells) | Cohort A |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort A | Experimental | 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. | - T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
|
Cohort B | Experimental | 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. | - T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
|
Cohort C | Experimental | 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. | - T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
|
Cohort D | Experimental | 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. | - T-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
|
Eligibility 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
Maximum Eligible Age: | 30 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: | 6 months |
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
Last Updated
March 25, 2021