Clinical trial NCT03186118: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: CD 19+ Acute Leukemia
Keywords: pediatric
young adult
acute lymphoblastic leukemia
CD 19
leukemia
chimeric antigen receptor
T cell
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed.
timeFrame: up to 6 months
measure: Determine the feasibility of deriving and administering a CD19t T-APC product
timeFrame: 28 days
Secondary outcomes:
measure: Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs
timeFrame: 6 months
measure: Duration of B cell aplasia in CD19t T-APC treated patients
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Colleen Annesley, MD
role: STUDY_CHAIR
References: