CD 19+ Acute Leukemia
Conditions
Keywords
pediatric, young adult, acute lymphoblastic leukemia, CD 19, leukemia, chimeric antigen receptor, T cell
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.
Interventions
BIOLOGICALT-cell Antigen Presenting Cells expressing truncated CD19 (T-APC)
Autologous CD4 and CD8 T cells transduced to express a truncated CD19 (CD19t) Transgene
Sponsors
Seattle Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed. | 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 | 28 days | Proportion of products successfully manufactured and infused |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs | 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 | up to 5 years | MPF from peripheral blood as a measure of B cell aplasia |
Countries
United States
Contacts
STUDY_CHAIRColleen Annesley, MD
Seattle Children's Hospital
Outcome results
None listed