Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12-29
SponsorRoberto Chiarle
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 12 months and < 30 years at the time of consent. The first patient on each dose level will need to be age ≥ 6 years old
Patients must have histologic verification of neuroblastoma at diagnosis or at relapse
Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment
Patients must have persistent/refractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol
Disqualifiers
Pregnant or nursing (lactating) women
Patients with uncontrolled active infection
Patients who are concurrently receiving other investigational agents
Patients who have received prior CART-cell or other gene-modified immune-effector cell therapy, are not eligible unless they are >8 weeks from time of infusion, have fully recovered from any associated toxicities and have documented lack of persistence of the product
Trial design
Design model
Sequential
Treatments tested in this trial
Autologous hALK.CAR T cells
Biological/VaccineAutologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor
Treatment groups
42 Participants
are divided into 1 treatment groupGroup A: Phase 1 Dose EscalationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase 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 years2
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 years3
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 yearsSecondary outcomes
1
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 years2
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 years3
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 years4
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 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Roberto Chiarle
Lead sponsor
Boston Children's Hospital
Sponsor institution
Boston Children's Hospital
Collaborator
Dana-Farber Cancer Institute
Collaborator
Source ClinicalTrials.gov