Clinical trial • Phase III • Oncology

Axicabtagene ciloleucel for Relapsed/Refractory Follicular lymphoma

Phase III trial of Axicabtagene ciloleucel for Relapsed/Refractory Follicular lymphoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Relapsed/Refractory Follicular lymphoma
Trial Stage
Phase III
Drug Modality
Cell therapy | Small molecule | Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
10-06-2024
First CTIS Authorization Date
23-07-2024

Trial design

Randomised, open-label, standard of care/comparator therapies include multiple approved products: bendamustine 100 mg powder for concentrate for solution for infusion (bendamustine hydrochloride) — intravenous; max daily dose listed 90 mg/m2 (product smpc referenced). revlimid 20 mg hard capsules (lenalidomide) — oral; max daily dose listed 20 mg. vincristine sulfate 1 mg/ml solution for injection or infusion (vincristine sulfate) — intravenous; max daily dose listed 2 mg. endoxana injection 1000 mg (cyclophosphamide) — intravenous; max daily dose listed 750 mg/m2. mabthera 500 mg concentrate for solution for infusion (rituximab) — intravenous; max daily dose listed 375 mg/m2. prednisolone 5 mg soluble tablets (prednisolone) — oral; dosing details present in product listing. doxorubicin teva 2 mg/ml concentrate for solution for infusion (doxorubicin hydrochloride) — intravenous; max daily dose listed 50 mg/m2. specific schedules/regimens are not specified in the ctis summary; dose maxima are taken from the listed product information.-controlled Phase III trial across 28 sites in Germany, Spain, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Standard of care/comparator therapies include multiple approved products: Bendamustine 100 mg powder for concentrate for solution for infusion (Bendamustine hydrochloride) — intravenous; max daily dose listed 90 mg/m2 (product SmPC referenced). Revlimid 20 mg hard capsules (Lenalidomide) — oral; max daily dose listed 20 mg. Vincristine Sulfate 1 mg/ml solution for injection or infusion (Vincristine sulfate) — intravenous; max daily dose listed 2 mg. Endoxana Injection 1000 mg (Cyclophosphamide) — intravenous; max daily dose listed 750 mg/m2. MabThera 500 mg concentrate for solution for infusion (Rituximab) — intravenous; max daily dose listed 375 mg/m2. Prednisolone 5 mg Soluble Tablets (Prednisolone) — oral; dosing details present in product listing. Doxorubicin Teva 2 mg/ml concentrate for solution for infusion (Doxorubicin hydrochloride) — intravenous; max daily dose listed 50 mg/m2. Specific schedules/regimens are not specified in the CTIS summary; dose maxima are taken from the listed product information.
Target Sample Size
75

Eligibility

Recruits 75 Vulnerable population selected (field 'isVulnerablePopulationSelected' = true). The provided CTIS record does not include detailed information on specific vulnerable groups, assent procedures, or explicit consent-by-proxy arrangements in the available fields/documents..

Pregnancy Exclusion
Females who are pregnant or breastfeeding
Vulnerable Population
Vulnerable population selected (field 'isVulnerablePopulationSelected' = true). The provided CTIS record does not include detailed information on specific vulnerable groups, assent procedures, or explicit consent-by-proxy arrangements in the available fields/documents.

Inclusion criteria

  • {"criterion_text":"- Histologically-confirmed follicular lymphoma (FL) (Grade 1, 2, or 3a)"}
  • {"criterion_text":"- Relapsed/refractory (R/r) disease after first-line chemoimmunotherapy and high-risk disease with relapse or progression within 24 months of the initial course of chemoimmunotherapy (ie, POD24), Or r/r disease after ≥ 2 prior systemic lines of therapy"}
  • {"criterion_text":"- Clinical indication for treatment."}
  • {"criterion_text":"- At least 1 measurable lesion per the Lugano Classification {Cheson 2014}"}
  • {"criterion_text":"- Adequate renal, hepatic, pulmonary, and cardiac function"}

Exclusion criteria

  • {"criterion_text":"- Presence of large B cell lymphoma or transformed FL"}
  • {"criterion_text":"- History or presence of a clincially significant central nervous system (CNS) disorder."}
  • {"criterion_text":"- History of autoimmune disease"}
  • {"criterion_text":"- Known history or CNS lymphoma involvement"}
  • {"criterion_text":"- Cardiac lymphoma involvement"}
  • {"criterion_text":"- History of clinically significant cardiac disease 6 months before randomization"}
  • {"criterion_text":"- Neuropathy greater than grade 2"}
  • {"criterion_text":"- Females who are pregnant or breastfeeding"}
  • {"criterion_text":"- Individuals of both genders who are not willing to practice birth control"}
  • {"criterion_text":"- Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, pleural/peritoneal/pericardial catheter, or Ommaya reservoirs). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted."}
  • {"criterion_text":"- Small lymphocytic lymphoma"}
  • {"criterion_text":"- Lymphoplasmacytic lymphoma"}
  • {"criterion_text":"- Full-thickness involvement of the gastric wall by lymphoma"}
  • {"criterion_text":"- FL Grade 3b"}
  • {"criterion_text":"- Prior CD19-targeted therapy"}
  • {"criterion_text":"- Prior CAR therapy or other genetically modified T-cell therapy"}
  • {"criterion_text":"- Uncontrolled fungal, bacterial, viral, or other infection"}
  • {"criterion_text":"- Active Infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- PFS, defined as the time from randomization to disease progression per the International Working Group Lugano Classification {Cheson 2014} as determined per a blinded central assessment, or death due to any cause.","definition_or_measurement_approach":"Progression-free survival (PFS) measured from randomization to disease progression per Lugano Classification (Cheson 2014) as determined by a blinded independent radiologic review committee (blinded central assessment), or death from any cause."}

Secondary endpoints

  • {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival (OS); no further definition provided in the CTIS record."}
  • {"endpoint_text":"- CR rate per Lugano Classification {Cheson 2014} as determined per a blinded central assessment","definition_or_measurement_approach":"Complete response (CR) rate defined per Lugano Classification (Cheson 2014), determined by blinded central assessment."}
  • {"endpoint_text":"- ORR (CR + PR per Lugano Classification {Cheson 2014}) as determined per a blinded central assessment","definition_or_measurement_approach":"Objective response rate (ORR = CR + PR) per Lugano Classification (Cheson 2014), determined by blinded central assessment."}
  • {"endpoint_text":"- DOR","definition_or_measurement_approach":"Duration of response (DOR); no additional definition provided in the CTIS record."}
  • {"endpoint_text":"- Duration of CR","definition_or_measurement_approach":"Duration of complete response (CR); no additional definition provided in the CTIS record."}
  • {"endpoint_text":"- EFS","definition_or_measurement_approach":"Event-free survival (EFS); no additional definition provided in the CTIS record."}
  • {"endpoint_text":"- TTNT","definition_or_measurement_approach":"Time to next treatment (TTNT); no additional definition provided in the CTIS record."}
  • {"endpoint_text":"- Incidence of adverse events (AEs) and clinically significant changes in safety laboratory values","definition_or_measurement_approach":"Incidence of AEs and clinically significant safety lab changes as recorded during the study; no further measurement approach specified."}
  • {"endpoint_text":"- Incidence of replication-competent retrovirus (RCR) detection in blood over time","definition_or_measurement_approach":"Detection of replication-competent retrovirus (RCR) in blood over time; specific assay or schedule not provided in the CTIS record."}
  • {"endpoint_text":"- Changes from baseline in the Global Health Status Quality of Life scale and the physical functioning domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) and the Low Grade NonHodgkin Lymphoma-20 (NHL-LG20)","definition_or_measurement_approach":"Changes from baseline in EORTC QLQ-C30 global health status and physical functioning domain and NHL-LG20; measurement via validated questionnaires as named."}
  • {"endpoint_text":"- Changes from baseline in the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) and visual analogue scale (VAS).","definition_or_measurement_approach":"Changes from baseline measured by the EQ-5D-5L index and the EQ VAS; no additional details provided."}

Recruitment

Planned Sample Size
142
Recruitment Window Months
91
Consent Approach
Informed consent is obtained using country-specific subject information and informed consent forms. Documents in the CTIS record include ICFs in German, Spanish, Italian and French (e.g. 'L1_DE_SIS-ICF_Adults_German', 'L1_ES_SIS-ICF_Main_Spanish', 'L1_IT_SIS-ICF_Main Adults_Italian', 'L1_FR_SIS-ICF_Main_French'). There are also pregnancy-specific information/ICF documents (e.g. 'L1_DE_SIS-ICF_Pregnancy_German', 'L1_ES_SIS-ICF_Pregnancy_Spanish') and a partner pregnancy follow-up form (Italy). The record does not provide explicit details on assent procedures for minors; ICFs shown are adult ICFs and language versions as listed above.

Methods

  • Recruitment arrangements placeholder documents (country-specific): Germany, Spain, Italy, France (documents titled 'Recruitment Procedure_Placeholder Document' and 'Recruitment Arrangements_Placeholder document').
  • Doctor-to-doctor recruitment letters (document: 'K2_FR_Recruitment Material_Dr to Dr Letter_French'). Target audience: clinicians (country: France).
  • Posters for participant recruitment (document: 'K2_FR_Recruitment Material_Poster_French'). Target audience: potential participants (country: France).
  • Site scout information / site-specific scout consent forms (documents named 'SIS-ICF_Scout' in German, French, etc.) indicating use of site scouts in recruitment (country-specific documents available).

Geography

Total Number Of Sites
28
Total Number Of Participants
142

Germany

Latest Decision Or Authorization Date
23-07-2024
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Universitaetsmedizin Goettingen
Department Name
Department for Hematology and Medical Oncology
Contact Person Name
Gerald Georg Wulf
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Zentrum Innere Medizin
Contact Person Name
Max Topp
Contact Person Email
Topp_M@ukw.de

Spain

Latest Decision Or Authorization Date
23-07-2024
Number Of Sites
9
Number Of Participants
75

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Contact Person Name
Fatima De la Cruz Vicente
Contact Person Email
fatimadelacruzv@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Hematology
Contact Person Name
Ana Maria Sureda Balari
Contact Person Email
asureda@iconcologia.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Hematology
Contact Person Name
Ana Jiménez Ubieto
Contact Person Email
anitiju@hotmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematology
Contact Person Name
Gloria Iacoboni García-Calvo
Contact Person Email
giacoboni@vhio.net
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Hematology
Contact Person Name
María José Terol Castera
Contact Person Email
mariajose.terol@uv.es
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Contact Person Name
Alejandro Martín García-Sancho
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Hematology
Contact Person Name
Mariana Bastos Oreiro
Site Name
Hospital Clinic De Barcelona
Department Name
Hematology
Contact Person Name
Armando López Guillermo
Contact Person Email
alopezg@clinic.cat
Site Name
Hospital Universitario 12 De Octubre (duplicate entry not assumed)
Department Name
Hematology

Italy

Latest Decision Or Authorization Date
05-08-2024
Number Of Sites
6
Number Of Participants
14

Sites

Site Name
Arcispedale S. M. Nuova
Department Name
Division of Hematology
Contact Person Name
Stefano Luminari
Contact Person Email
stefano.luminari@ausl.re.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Department Name
Oncology and Hematology department
Contact Person Name
Silvia Ferrari
Contact Person Email
s.ferrari@asst-pg23.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
Section “Terapia Cellulare e CAR -T”
Contact Person Name
Stefania Bramanti
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Dept. of Medical Oncology and Hematology
Contact Person Name
Paolo Corradini
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Lymphoma Unit
Contact Person Name
Andres Josè Maria Ferreri
Contact Person Email
ferreri.andres@hsr.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS
Department Name
Dipartimento Malattie Oncologiche ed Ematologiche
Contact Person Name
Pier Lugi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it

France

Latest Decision Or Authorization Date
14-01-2026
Number Of Sites
11
Number Of Participants
49

Sites

Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Service d’Hématologie
Contact Person Name
Roch Houot
Contact Person Email
roch.houot@chu-rennes.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service d’Hématologie clinique et Thérapie cellulaire
Contact Person Name
Kamal Bouabdallah
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Département d’Hématologie clinique
Contact Person Name
Guillaume Cartron
Contact Person Email
g-cartron@chu-montpelier.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Maladies du Sang
Contact Person Name
Franck Morschhauser
Site Name
Institut Paoli Calmettes
Department Name
Institut Paoli-Calmettes
Contact Person Name
Gabriel Brisou
Contact Person Email
brisoug@ipc.unicancer.fr
Site Name
Hospices Civils De Lyon
Department Name
Service d’Hématologie Clinique
Contact Person Name
Emmanuel Bachy
Contact Person Email
emmanuel.bachy@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Service d’Hématologie et Thérapie Cellulaire and Centre d’inestigations cliniques (CIC)
Contact Person Name
Stephanie Guidez
Site Name
Hopitaux Universitaires Pitie Salpetriere
Department Name
Service d’Hématologie
Contact Person Name
Sylvain Choquet
Contact Person Email
sylvain.choquet@aphp.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Service d’Hématologie Clinique
Contact Person Name
Cédric Rossi
Contact Person Email
cedric.rossi@chu-dijon.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Unité Hémopathies Lymphoïdes
Contact Person Name
Jehan Dupuis
Contact Person Email
jehan.dupuis@aphp.fr
Site Name
Centre Henri Becquerel
Department Name
Département d’Hématologie Clinique
Contact Person Name
Fabrice Jardin
Contact Person Email
jardin@chb.unicancer.fr

Sponsor

Primary sponsor

Full Name
Kite Pharma Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Regulatory (preparation of applications to CA and ethics committee); Site initiation and set-up; Monitoring

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code '7' (role code provided in CTIS record; specific textual role not provided)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central Laboratory Services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"IVRS30 – treatment randomisation","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Regulatory (e.g. preparation of applications to CA and ethics committee); Site initiation and set-up; Monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central Imaging","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
YESCARTA 0.4 – 2 x 10e8 cells dispersion for infusion
Active Substance
Axicabtagene ciloleucel
Modality
Cell therapy
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/18/1299/001 listed)
Orphan Designation
Yes
Maximum Dose
2000000 (DF dosage form) as listed in product entry
Investigational Product Name
Bendamustine 100mg Powder for Concentrate for Solution for Infusion
Active Substance
Bendamustine hydrochloride
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation PA1986/121/002 listed)
Maximum Dose
90 mg/m2 (max daily dose listed)
Investigational Product Name
Revlimid 20 mg hard capsules
Active Substance
Lenalidomide
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation EU/1/07/391/009 listed)
Maximum Dose
20 mg (max daily dose listed)
Investigational Product Name
Vincristine Sulfate 1 mg/ml Solution for Injection or Infusion
Active Substance
Vincristine sulfate
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation PA 0822/232/001 listed)
Maximum Dose
2 mg (max daily dose listed)
Investigational Product Name
Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion
Active Substance
Doxorubicin hydrochloride
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation PA 749/083/1 listed)
Maximum Dose
50 mg/m2 (max daily dose listed)
Investigational Product Name
Endoxana Injection 1000 mg Powder for Solution for Injection
Active Substance
Cyclophosphamide
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation entry listed)
Maximum Dose
750 mg/m2 (max daily dose listed)
Investigational Product Name
Prednisolone 5 mg Soluble Tablets
Active Substance
Prednisolone
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation PL 17780/0949 listed)
Maximum Dose
40 mg (max daily dose listed in product entry)
Investigational Product Name
MabThera 500 mg concentrate for solution for infusion
Active Substance
Rituximab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/98/067/002 listed)
Maximum Dose
375 mg/m2 (max daily dose listed)
Combination Treatment
Yes

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