Clinical trial NCT02445222: CAR-T Long Term Follow Up (LTFU) Study
Official title: Long Term Follow-Up of Patients Exposed to Lentiviral-Based CAR T-Cell Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Long Term Safety of Patients Receiving CAR-T in an Eligible Clinical Trial or Managed Access Program
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2015-05-15
Enrollment: 1400
Sex: ALL
Minimum age (years): 0
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Per Health Authorities guidelines for gene therapy medicinal products that utilize integrating vectors (e.g. lentiviral vectors), long term safety and efficacy follow up of treated patients is required. The purpose of this study is to monitor all patients exposed to CAR-T therapied for 15 years following their last CAR-T (e.g. CTL019) infusion to assess the risk of delayed adverse events (AEs), monitor for replication competent lentivirus (RCL) and assess long-term efficacy, including vector persistence.

Detailed description: Patients are enrolled following completion or early discontinuation from a Novartis sponsored or supported study of CAR T-Cell treatment. Patients will be followed for 15 years post treatment from the last treatment. They will be monitored for safety and efficacy within the primary treatment protocols for the protocol defined duration. Patients can drop off treatment protocols at any time to enter this long term Follow up study. Patients discontinuing from the primary treatment protocols for any reason will be enrolled in this long term follow up (LTFU). This will allow collecting data on long term safety and efficacy (as applicable) as mandated by the health authorities of all patients treated with CAR-T therapy within the concept of a single protocol.

Collection of such long term effects of CAR-T cell therapy will help to further define the risk-benefit profile of CAR-T Therapies.

Eligibility criteria: Inclusion Criteria:

* All patients who have received a CAR-T therapy and completed or discontinued early from a Novartis sponsored treatment protocol that utilized CAR-T cells or from any CAR-T trial sponsored by the University of Pennsylvania with which Novartis has a contractual agreement to co-develop the CAR technology.
* Patients who have provided informed consent for the long term follow up study prior to their study participation .

Exclusion Criteria:

* There are no specific exclusion criteria for this study.

Primary outcomes:
measure: Percentage of patients with certain events (see description)
timeFrame: at M3 post treatment, M6, M9, M12 and then, every 6M up to year 5, yearly until year 15.
Secondary outcomes:
measure: Percentage of patients with detectable CAR transgene levels in peripheral blood by q-PCR at pre- specified time points
timeFrame: at M3 post treatment, M6, M9, M12 and every 6M up to year 5, yearly until year 15.
measure: Percentage of patients with detectable RCL by VSV-G
timeFrame: at M3 post treatment then M6, M9, M12 and every 6M up to year 5, yearly until year 15
measure: Percentage of patients who relapse or progress among patients who had not relapsed or progressed at study entry/re-entry;Incidence of death
timeFrame: at M3 post treatment then M6, M9, M12 and every 6M up to year 5, yearly until year 15.
measure: B- and T- lymphocyte count
timeFrame: at M3 post treatment then M6, M9, M12 and every 6M up to year 5, yearly until year 15.
measure: Height and weight, Tanner staging, menstruation status
timeFrame: at M3 post treatment then M6, M12 and every year until year 15.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Childrens Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center, Hematology & Oncology
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center SC
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Cente
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System SC CTL019
state: Michigan
city: Detroit
country: United States
facility: Wayne State University-Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital SC
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke Unversity Medical Center SC - CTL019B2205J
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio ST Compr Cancer Ctr James Hosp
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Childrens Hosp of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UTSW/Children's Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center SC
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Clinical Trials Office
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Murdoch
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Herston
country: Australia
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
state: CS
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Esplugues De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: