Clinical trial • Phase I/II • Oncology

RAPCABTAGENE AUTOLEUCEL for High-risk large B-cell lymphoma | Chronic lymphocytic leukemia | Small lymphocytic lymphoma | Diffuse large B-cell lymphoma | Acute lymphoblastic leukemia

Phase I/II trial of RAPCABTAGENE AUTOLEUCEL for High-risk large B-cell lymphoma | Chronic lymphocytic leukemia | Small lymphocytic lymphoma | Diffuse larg…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
High-risk large B-cell lymphoma | Chronic lymphocytic leukemia | Small lymphocytic lymphoma | Diffuse large B-cell lymphoma | Acute lymphoblastic leukemia
Trial Stage
Phase I/II
Drug Modality
Cell therapy | Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
27-06-2024
First CTIS Authorization Date
29-07-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial in Germany, Spain, France and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, Dose-escalation design in Phase I to identify the Recommended Dose with DLT assessment during the first 28 days post-infusion; manufacture success rate assessed; interim/adaptive elements relate to dose escalation and recommended dose determination (specific stopping rules or statistical adaptive algorithms not stated).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
101

Eligibility

Recruits 101 Vulnerable population flag is set (isVulnerablePopulationSelected = true). The available record does not provide detailed text describing consent/assent procedures for vulnerable participants; specific assent/parental consent handling is not provided in the extracted fields..

Vulnerable Population
Vulnerable population flag is set (isVulnerablePopulationSelected = true). The available record does not provide detailed text describing consent/assent procedures for vulnerable participants; specific assent/parental consent handling is not provided in the extracted fields.

Inclusion criteria

  • {"criterion_text":"- 3L+ DLBCL: Relapsed or refractory disease having received 2 or more lines of therapy, including anti-CD20 and anthracycline-based chemotherapy, and either having progressed (or relapsed) after autologous HSCT or being ineligible/not consenting to the procedure. Measurable disease at time of enrollment.\n- ALL: r/r CD19-positive ALL with morphologic disease in the bone marrow (≥ 5% blasts) and including at least 1 of the following: • After allogeneic HSCT • After 2 or more lines of treatment • Primary refractory disease • First relapse occurring within 12 months from first remission • Patients with Philadelphia chromosome-positive ALL must have failed at least 2 different tyrosine kinase inhibitors.\n- 1L HR LBCL: - Considered to be high-risk based on at least 1 of the following at diagnosis: • IPI score of 3, 4 or 5 • MYC and BCL2 and/or BCL6 rearrangement (DH/TH).\n- 1L HR LBCL: - Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received DA-EPOCH-R.\n- 1L HR LBCL: - Participants must have a positive PET per Lugano classification (Deauville PET score of 4 or 5 and an overall response of PR/SD) after 2 cycles of frontline CIT. Note: Patient’s with Deauville PET score of 5 and overall response of PD, or with Deauville PET score of 1, 2, or 3 and overall response of CR, are not eligible for this trial."}

Exclusion criteria

  • {"criterion_text":"- ALL: allogeneic HSCT within 12 weeks prior to screening\n- Prior CD19-directed therapy with the exception of blinatumomab for patients with ALL\n- Prior administration of a genetically modified cellular product\n- 3L+ DLBCL with primary CNS lymphoma\n- 3L+ DLBCL: prior allogeneic HSCT"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Incidence and nature of Dose Limiting Toxicities during the first 28 days after rapcabtagene autoleucel infusion (Dose Escalation part only) Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.","definition_or_measurement_approach":"Incidence and nature of Dose Limiting Toxicities during the first 28 days after infusion (Dose Escalation part only); incidence and severity of AEs and SAEs including lab values, ECG and vital signs following rapcabtagene autoleucel infusion."}
  • {"endpoint_text":"- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Ibrutinib dose modifications following rapcabtagene autoleucel infusion.","definition_or_measurement_approach":"Assessment of ibrutinib dose modifications after rapcabtagene autoleucel infusion (Phase I)."}
  • {"endpoint_text":"- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Manufacture success rate (defined as number of participants with product that meets release specifications and at or above the planned target dose divided by total number of patients enrolled).","definition_or_measurement_approach":"Manufacture success rate defined as number of participants with product meeting release specifications at/above planned target dose divided by total enrolled."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.","definition_or_measurement_approach":"Complete response rate (CRR) defined as best overall response (BOR) of complete response (CR) after infusion per Lugano criteria."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.","definition_or_measurement_approach":"Complete response rate (CRR) defined as BOR of CR after infusion per Lugano criteria."}

Secondary endpoints

  • {"endpoint_text":"- Phase I part - CLL/SLL, 3L+ DLBCL and ALL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.","definition_or_measurement_approach":"Quantification of rapcabtagene autoleucel transgene concentrations by qPCR over time in peripheral blood and relevant tissues."}
  • {"endpoint_text":"- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.","definition_or_measurement_approach":"Characterize incidence and prevalence of pre-existing and treatment-induced cellular and humoral immunogenicity."}
  • {"endpoint_text":"- Phase I part - CLL/SLL: - BOR of CR/PR per iwCLL response criteria Duration of response (DOR), i.e., time from first achievement of CR/PR after rapcabtagene autoleucel infusion until first documented disease progression or death due to any cause.","definition_or_measurement_approach":"BOR of CR/PR per iwCLL criteria; DOR defined as time from first CR/PR after infusion to documented progression or death."}
  • {"endpoint_text":"- Phase I part - 3L+ DLBCL: - BOR of CR/PR as per Lugano criteria. Complete response rate (CRR) at months 3 and 6 DOR.","definition_or_measurement_approach":"BOR of CR/PR per Lugano; CRR at months 3 and 6; DOR measured from first CR/PR to progression or death."}
  • {"endpoint_text":"- Phase I part - ALL: - BOR of CR/Cri. Disease response (CR/Cri) at month 3 and 6. DOR, defined as the time from achievement of CR or Cri to relapse or death due to any cause. EFS, defined as the date from rapcabtagene autoleucel infusion to the earliest date of relapse after CR/Cri, treatment failure (defined as failure to achieve CR/Cri within 12 weeks of infusion), or death due to any cause.","definition_or_measurement_approach":"BOR of CR/Cri; disease response at months 3 and 6; DOR and EFS defined as stated."}
  • {"endpoint_text":"- Phase I part – ALL: - MRD negative status by flow cytometry.","definition_or_measurement_approach":"MRD negativity assessed by flow cytometry."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria.","definition_or_measurement_approach":"ORR defined as BOR of CR or PR per Lugano criteria."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - CRR at months 3 and 6.","definition_or_measurement_approach":"CRR measured at months 3 and 6 post-infusion."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Duration of response (DOR), defined as time from first CR/PR to first documented progression or death due to any cause.","definition_or_measurement_approach":"DOR defined as time from first CR/PR to progression or death."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause.","definition_or_measurement_approach":"PFS measured from infusion to progression or death."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause.","definition_or_measurement_approach":"OS measured from infusion date to death from any cause."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.","definition_or_measurement_approach":"Safety assessed by incidence/severity of AEs/SAEs and changes in labs, ECG, vital signs."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.","definition_or_measurement_approach":"qPCR quantification of transgene concentrations over time in peripheral blood and tissues."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.","definition_or_measurement_approach":"Assessment of pre-existing and treatment-induced immunogenicity (cellular and humoral)."}
  • {"endpoint_text":"- Phase II part – 3L+ DLBCL: - Time from apheresis completion until return of rapcabtagene autoleucel product to the clinic or hospital.","definition_or_measurement_approach":"Measure elapsed time from apheresis completion to return of product to clinic/hospital (vein-to-door time)."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria.","definition_or_measurement_approach":"ORR defined as BOR of CR/PR per Lugano."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - CRR at months 6 and 12.","definition_or_measurement_approach":"CRR measured at months 6 and 12."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Duration of response (DOR). Defined as time from first CR/PR to first documented progression or death due to any cause.","definition_or_measurement_approach":"DOR defined as time from first CR/PR to progression or death."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause.","definition_or_measurement_approach":"PFS measured from infusion to progression or death."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Event-free survival (EFS) defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause.","definition_or_measurement_approach":"EFS defined as time from infusion to earliest of progression, new anti-lymphoma therapy start, biopsy-proven residual disease at/after month 6, or death."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause.","definition_or_measurement_approach":"OS measured from infusion date to death."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Within each subgroup: CRR, ORR CRR at months 6 and 12 DOR, PFS, EFS, OS","definition_or_measurement_approach":"Efficacy endpoints (CRR, ORR, CRR at months 6/12, DOR, PFS, EFS, OS) evaluated within specified subgroups."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.","definition_or_measurement_approach":"Safety evaluation by incidence/severity of AEs/SAEs and lab/ECG/vitals changes."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.","definition_or_measurement_approach":"qPCR assessment of transgene concentrations over time."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.","definition_or_measurement_approach":"Assessment of immunogenicity (pre-existing and treatment-induced, cellular and humoral)."}
  • {"endpoint_text":"- Phase II part – 1L HR LBCL: - Time from apheresis completion until return of rapcabtagene autoleucel product to the clinic or hospital.","definition_or_measurement_approach":"Measure vein-to-door time from apheresis completion to product return to clinic/hospital."}

Recruitment

Planned Sample Size
101
Recruitment Window Months
98
Consent Approach
Informed consent is obtained using subject information and informed consent forms (ICFs) for adult participants. Multiple language versions of ICFs are available (English, German, Spanish, French, Italian) as indicated by the ICF documents. No specific details on assent procedures or consent for minors are provided in the extracted record.

Geography

Total Number Of Sites
22
Total Number Of Participants
142

Germany

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
01-08-2024
Processing Time Days
17
Number Of Sites
3
Number Of Participants
14

Sites

Site Name
Universitaet Leipzig
Department Name
1002 :Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
Contact Person Name
Vladan Vucinic
Site Name
Universitaetsklinikum Essen AöR
Department Name
1003 :Klinik für Hämatologie und Stammzelltransplantation
Contact Person Name
Bastian von Tresckow
Site Name
Goethe University Frankfurt
Department Name
1001: Medizinische Klinik II, Hämatologie / Onkologie
Contact Person Name
Gesine Bug
Contact Person Email
Gesine.bug@kgu.de

Spain

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
29-07-2024
Processing Time Days
14
Number Of Sites
10
Number Of Participants
80

Sites

Site Name
Institut Catala D'oncologia
Department Name
#4007:Hematología Clínica
Contact Person Name
Juan Manuel Sancho Cia
Contact Person Email
jsancho@iconcologia.net
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
#4002:Hematología
Contact Person Name
Cristina Blazquez Goni
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
#4000:Hematología
Contact Person Name
Javier Briones Meijide
Contact Person Email
jbriones@santpau.cat
Site Name
Hospital Universitario Reina Sofia
Department Name
#4006:Hematología
Contact Person Name
Estefania Garcia Torres
Site Name
Hospital Universitario 12 De Octubre
Department Name
#4005:Oncología
Contact Person Name
Joaquin Martinez Lopez
Contact Person Email
jmarti01@med.ucm.es
Site Name
Hospital Clinico Universitario De Valencia
Department Name
#4004:Hematología
Contact Person Name
Carlos Solano Vercet
Contact Person Email
solano_car@gva.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
#4003:Hematología
Contact Person Name
Mi Kwon
Contact Person Email
mi.kwon@salud.madrid.org
Site Name
Institut Catala D'oncologia (L'hospitalet de Llobregat)
Department Name
#4009:Hematología Clínica
Contact Person Name
Ana Maria Sureda Balari
Contact Person Email
asureda@iconcologia.net
Site Name
Hospital Universitario De Salamanca
Department Name
#4008:Hematología
Contact Person Name
Alejandro Martin Garcia Sancho
Site Name
Hospital Universitari Vall D Hebron
Department Name
4001:Hematología
Contact Person Name
Pere Barba Sunol
Contact Person Email
perebarbasunolpbarba@vhio.net

France

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
01-08-2024
Processing Time Days
17
Number Of Sites
5
Number Of Participants
18

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
#6003: Hemato-Oncologie
Contact Person Name
Catherine THIEBLEMONT
Contact Person Email
Catherine.thieblemont@aphp.fr
Site Name
Institut Paoli Calmettes
Department Name
#6001: Hematologie
Contact Person Name
Didier BLAISE
Contact Person Email
blaised@ipc.unicancer.fr
Site Name
Assistance Publique Hopitaux De Paris (unit for AYA)
Department Name
#6002: Hematologie – Unite d’hematologie Adolescents et Jeunes Adultes
Contact Person Name
Nicolas BOISSEL
Contact Person Email
Nicolas.boissel@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
#6004: Hematologie
Contact Person Name
Roch HOUOT
Contact Person Email
Roch.houot@chu-rennes.fr
Site Name
Hospices Civils De Lyon
Department Name
#6000: Hematologie clinique
Contact Person Name
Emmanuel BACHY
Contact Person Email
Emmanuel.bachy@chu-lyon.fr

Austria

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
05-08-2024
Processing Time Days
21
Number Of Sites
1
Number Of Participants
12

Sites

Site Name
Medical University Of Vienna
Department Name
Department of Hematology
Contact Person Name
Ulrich Jaeger
Contact Person Email
ulrich.jaeger@meduniwien.ac.at

Italy

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
05-08-2024
Processing Time Days
21
Number Of Sites
3
Number Of Participants
18

Sites

Site Name
Ospedale San Raffaele S.r.l.
Department Name
3000: U.O Ematologia e Trapianto Midollo Osseso (UTMO)
Contact Person Name
Fabio Ciceri
Contact Person Email
ciceri.fabio@hsr.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Department Name
3002: U.O.C. di Ematologia
Contact Person Name
Giuseppe Gritti
Contact Person Email
g.gritti@asst-pg23.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
3004: U.O. di Oncologia Medica ed Ematologia
Contact Person Name
Stefania Bramanti

Sponsor

Primary sponsor

Full Name
Novartis Pharma AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
sponsorDuties codes: [1]; contact: Triona.PriceSmith1@docsglobal.com
Name
IQVIA Limited
Responsibilities
sponsorDuties codes: [15]; Endpoint adjudication & management of independent review committee related activities; contact: eu_clinical_trials_information@iqvia.com
Name
Parexel International (IRL) Limited
Responsibilities
sponsorDuties codes: [12]; contact: Clinicaltrial.Enquiries@parexel.com
Name
Syneos Health Inc.
Responsibilities
sponsorDuties codes: [1]; contact: sm_ctis@syneoshealth.com

Third parties

  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties codes: [4]; email: GlobalNovartisTeam@labcorp.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [1]; email: Triona.PriceSmith1@docsglobal.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]; email: timothy.hamilton@bioagilytix.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"sponsorDuties codes: [4]; email: trial.support@navigatebp.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Phardis S.r.l.","duties_or_roles":"sponsorDuties codes: [15]; value: Local equipment storage; email: conti.monica@difarco.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"sponsorDuties codes: [8]; email: andreas.raffeiner@studien-monitor.at","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [15]; value: Endpoint adjudication & management of independent review committee related activities; email: eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"sponsorDuties codes: [3]; email: Hello@calyx.ai","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties codes: [4]; email: info@cellcarta.com","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: [1]; email: sm_ctis@syneoshealth.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: [12]; email: Clinicaltrial.Enquiries@parexel.com","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Kayentis","duties_or_roles":"sponsorDuties codes: [15]; value: ePROs; email: projectmanagement@kayentis.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"India","full_name":"Parexel International Services India Private Limited","duties_or_roles":"sponsorDuties codes: [5]; email: anand.tendulkar@parexel.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioagilytix Labs LLC (Boston address)","duties_or_roles":"sponsorDuties codes: [4]; email: CustomerServices@BioAgilytix.com","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"sponsorDuties codes: [4]; email: BA_Submissions@iconplc.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"sponsorDuties codes: [4]; email: regulatory@adaptivebiotech.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"sponsorDuties codes: [13]; email: support@bioclinica.com","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"sponsorDuties codes: [15]; value: CCI; email: nancy.annunziato@medable.com","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
YTB323
Active Substance
RAPCABTAGENE AUTOLEUCEL
Modality
Cell therapy
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus=1 (as recorded in productDictionaryInfo)
Investigational Product Name
IBRUTINIB
Active Substance
IBRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
prodAuthStatus=2 (as recorded in productDictionaryInfo)
Orphan Designation
Yes
Combination Treatment
Yes

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