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

CD 19+ Acute Leukemia Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03186118
• Other study ID #: PLAT-03
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 4, 2017
• Est. completion date: July 2033

Study information

• Verified date: June 2023
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: July 2033
• Est. primary completion date: September 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• CD 19+ Acute Leukemia
• Leukemia

Intervention

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

Locations

Country	Name	City	State
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The adverse events associated with one or multiple CD19t T-APC product infusions will be assessed.	Type, frequency, severity, and duration of adverse events will be summarized	up to 6 months
Primary	Determine the feasibility of deriving and administering a CD19t T-APC product	Proportion of products successfully manufactured and infused	28 days
Secondary	Quantification of changes in the number of CAR T cells in peripheral blood before and after receiving CD19t T-APCs	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	6 months
Secondary	Duration of B cell aplasia in CD19t T-APC treated patients	MPF from peripheral blood as a measure of B cell aplasia	up to 5 years