This Phase 1/2 trial aims to determine the safety and feasibility of administration of autologous chimeric antigen receptor (CAR) T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor in pediatric subjects with relapsed or refractory neuroblastoma (NB). The trial will be conducted in two phases: Phase 1 will determine the maximum tolerated dose (MTD) of autologous hALK.CAR T cells using a 3+3 dose escalation design. Phase 2 will be an expansion phase to determine rates of response to hALK.CAR T cells.
This study consists of two phases. The primary objectives of Phase 1 and Phase 2 are: Phase 1: * To identify the maximum tolerated dose (MTD) of autologous hALK.CAR T cells, and the recommended phase 2 dose (RP2D) in participants with relapsed/refractory high-risk neuroblastoma. * To evaluate the feasibility of manufacturing autologous hALK.CAR T cells. Phase 2: To estimate the complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of participants with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor
Boston Children's Hospital
Boston, Massachusetts, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGPhase 1: Determine the Maximum Tolerated Dose (MTD) of hALK.CAR T cells
The Maximum Tolerated Dose (MTD) of hALK.CAR T cells will be determined by measuring the incidence of dose limiting toxicities (DLT) following administration of the hALK.CAR T cell product using a 3+3 dose escalation design.
Time frame: 5 years
Phase 1: Evaluate Manufacturing Feasibility of hALK.CAR T cells
Manufacturing feasibility will be evaluated as the proportion of patients undergoing leukapheresis who achieve manufacturing of a hALK.CAR T cell product that meets release criteria.
Time frame: 5 years
Phase 2: Estimate Response Rates
The complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of subjects with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells will be estimated.
Time frame: Up to 5 years
Phase 1: Estimate Response Rates
The complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of subjects with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells in the Phase 1 cohort will be estimated.
Time frame: 5 years
Estimate Progression Free Survival and Overall Survival
To estimate the progression free survival (PFS) and overall survival (OS) rates of subjects with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells.
Time frame: 5 years
Evaluate Patient-Reported Symptoms
Patient-reported symptoms of interest (including mood, gastrointestinal and pain symptoms) will be measured in subjects treated with hALK.CAR T cells using the Ped-PRO-CTCAE v.1 inventory prior to and until 2 years after hALK.CAR T cell infusion
Time frame: Up to 5 years
Persistence of hALK.CAR T cells
Persistence of hALK.CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis to detect and quantify survival of hALK.CAR T cells in the peripheral blood over time.
Time frame: Up to 5 years
Cytokine levels in the peripheral blood
Activity of hALK.CAR T cells will be assessed by measuring cytokine levels in the peripheral blood over time
Time frame: 5 years
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