Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma

Relapsed/Refractory Follicular Lymphoma Clinical Trial

— ZUMA-22  

Official title:

A Phase 3 Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Follicular Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05371093
• Other study ID #: KT-US-473-0133
• Secondary ID: 2021-003260-28
• Status: Recruiting
• Phase: Phase 3
• Start date: September 12, 2022
• Est. completion date: October 2030

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: Medical Information
• Phone: 844-454-5483(1-844-454-KITE)
• Email: medinfo[@]kitepharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma

Description:

Five years after the last study participant is randomized, participants who have received axicabtagene ciloleucel will transition to a separate Long-term Follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: October 2030
• Est. primary completion date: October 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically-confirmed follicular lymphoma (FL) (Grade 1, 2, or 3a)

• 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

• Clinical indication for treatment.

• At least 1 measurable lesion per the Lugano Classification {Cheson 2014}

• Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

• Presence of large B cell lymphoma or transformed FL

• Small lymphocytic lymphoma

• Lymphoplasmacytic lymphoma

• Full-thickness involvement of the gastric wall by lymphoma

• FL Grade 3b

• Prior CD19-targeted therapy

• Prior CAR therapy or other genetically modified T-cell therapy

• Uncontrolled fungal, bacterial, viral, or other infection

• Active Infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus

• History or presence of a clincially significant central nervous system (CNS) disorder.

• History of autoimmune disease

• Known history or CNS lymphoma involvement

• Cardiac lymphoma involvement

• History of clinically significant cardiac disease 6 months before randomization

• Neuropathy greater than grade 2

• Females who are pregnant or breastfeeding

• Individuals of both genders who are not willing to practice birth control

• 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Relapsed/Refractory Follicular Lymphoma

Intervention

Biological:
• Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Drug:
• Cyclophosphamide
Administered intravenously
• Fludarabine
Administered intravenously
• Lenalidomide
Administered orally
• Rituximab
Administered intravenously
• Doxorubicin
Administered intravenously
• Vincristine
Administered intravenously
• Prednisone
Administered orally
• Bendamustine
Administered intravenously

Locations

Country	Name	City	State
France	Hopital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	Hôpital Claude Huriez-CHU de Lille	Lille cedex
France	Institut Paoli-Calmettes	Marseille
France	Hopital Saint Eloi	Montpellier
France	Hopital Pitie-Salpetriere	Paris
France	CHU Bordeaux - Hospital Haut-Leveque - Centre Francois Magendie	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Poitiers	Poitiers
France	Hopital Pontchaillou - CHU Rennes	Rennes
France	Centre Henri Becquerel	Rouen
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitatsklinikum Koln Klinik I fur Innere Medizin	Cologne
Germany	Universitatsmedizin Gottingen	Göttingen
Germany	Universitat Leipzig Herzzentrum GmbH	Leipzig
Germany	Universitatsklinikum Ulm	Ulm
Germany	Universitatsklinikum Koln Klinik I fur Innere Medizin	Wuerzburg
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedallero-Universitaria di Bologna Policlinico Sant'Orsola-Malpighi	Bologna
Italy	IRCCS Ospedale Policlinico San Martino Padiglione Ex-Isolamento/IST/Padiglione	Genova
Italy	Fondazione IRCCS - Istituto Nazionale Tumori	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Istituto Clinico Humanitas-IRCCS	Rozzano
Japan	Hyogo Medical University Hospital	Hyogo
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	Tohoku University Hospital	Miyagi
Japan	Okayama University Hospital	Okayama
Japan	Osaka University Hospital	Osaka
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynolds (ICO L'Hospitalet)	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
United Kingdom	University Hospital Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	The University Hospital Southampton NHS Foundation Trust	Southampton
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Novant Health Cancer Institute Hematology - Charlotte	Charlotte	North Carolina
United States	Oncology_Hematology Care Clinical Trials, LLC	Cincinnati	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	Prisma Health - Upstate	Greenville	South Carolina
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	TriStar Centennial Medical Center - Cell Processing	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	UC Irvine Health	Orange	California
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Stanford Health Care	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	The University of Kansas Hospital	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Japan,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to 5 years
Secondary	Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification	CR rate is defined as the proportion of participants with best overall response of CR during the study prior to any subsequent off-protocol anti-follicular lymphoma (FL) therapy.	Up to 5 years
Secondary	Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification	Objective response rate is defined as the proportion of participants with best overall response of either a complete response or a partial response during the study prior to any subsequent off-protocol anti-FL therapy.	Up to 5 years
Secondary	Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification	DOR is defined as the time from first objective response to disease progression or death from any cause.	Up to 5 years
Secondary	Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification	Duration of CR is defined as the time from first CR to disease progression or death from any cause.	Up to 5 years
Secondary	Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification	EFS is defined as the time from randomization to the earliest date of disease progression, the initiation of subsequent off-protocol anti-FL therapy, or death from any cause.	Up to 5 years
Secondary	Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start of subsequent off-protocol anti-lymphoma therapy or death from any cause.	Up to 5 years
Secondary	Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		Randomization up to 5 years plus 30 days
Secondary	Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values		Randomization up to 5 years plus 30 days
Secondary	Percentage of Participants with Replication-competent Retrovirus in Blood Over time		Up to 5 years
Secondary	Change From Baseline in the Global Health Status Quality of Life Scale of the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30)	The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Secondary	Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30	The EORTC-QLQ-C30) is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Secondary	Change From Baseline in the Global Health Status Quality of Life Scale of the Low Grade Non-Hodgkin Lymphoma-20 (NHL-LG20)	The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Secondary	Change From Baseline in the Physical Functioning Domain of the NHL-LG20	The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, up to 5 years
Secondary	Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L)	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.	Baseline, up to 5 years
Secondary	Changes From Baseline in the Visual Analog Scale (VAS) Scores	The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). Higher scores indicate better health.	Baseline, up to 5 years

External Links

•   Gilead Clinical Trials Website