Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma (ZUMA-22)

• ClinicalTrials.gov Identifier: NCT05371093
• Recruitment Status: Recruiting
• First Posted: May 12, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

Tracking Information

• First Submitted Date: May 9, 2022
• First Posted Date: May 12, 2022
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: September 12, 2022
• Estimated Primary Completion Date: October 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2022)

Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]

PFS is defined as the time from randomization to disease progression or death due to any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 28, 2023)

• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  OS is defined as the time from randomization to death from any cause.
• Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  DOR is defined as the time from first objective response to disease progression or death from any cause.
• Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  Duration of CR is defined as the time from first CR to disease progression or death from any cause.
• Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Time to Next Treatment (TTNT) [ Time Frame: Up to 5 years ]
  TTNT is defined as the time from randomization to the start of subsequent off-protocol anti-lymphoma therapy or death from any cause.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Randomization up to 5 years plus 30 days ]
• Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values [ Time Frame: Randomization up to 5 years plus 30 days ]
• Percentage of Participants with Replication-competent Retrovirus in Blood Over time [ Time Frame: Up to 5 years ]
• 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) [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30 [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Global Health Status Quality of Life Scale of the Low Grade Non-Hodgkin Lymphoma-20 (NHL-LG20) [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Physical Functioning Domain of the NHL-LG20 [ Time Frame: Baseline, up to 5 years ]
  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.
• Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) [ Time Frame: Baseline, up to 5 years ]
  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.
• Changes From Baseline in the Visual Analog Scale (VAS) Scores [ Time Frame: Baseline, up to 5 years ]
  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.

Original Secondary Outcome Measures (submitted: May 9, 2022)

• Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  DOR is defined as the time from first objective response to disease progression or death from any cause.
• Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  Duration of CR is defined as the time from first CR to disease progression or death from any cause.
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  OS is defined as the time from randomization to death from any cause.
• Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification [ Time Frame: Up to 5 years ]
  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.
• Time to Next Treatment (TTNT) [ Time Frame: Up to 5 years ]
  TTNT is defined as the time from randomization to the start of new off-protocol anti-FL therapy or death from any cause.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Randomization up to 5 years plus 30 days ]
• Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values [ Time Frame: Randomization up to 5 years plus 30 days ]
• 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) [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30 [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Global Health Status Quality of Life Scale of the Low Grade Non-Hodgkin Lymphoma-20 (NHL-LG20) [ Time Frame: Baseline, up to 5 years ]
  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.
• Change From Baseline in the Physical Functioning Domain of the NHL-LG20 [ Time Frame: Baseline, up to 5 years ]
  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.
• Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) [ Time Frame: Baseline, up to 5 years ]
  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.
• Changes From Baseline in the Visual Analog Scale (VAS) Scores [ Time Frame: Baseline, up to 5 years ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma
• 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
• Brief Summary: The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed/Refractory Follicular Lymphoma

Intervention

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

  • Yescarta®
  • axi-cel
• Drug: Cyclophosphamide
  Administered intravenously
• Drug: Fludarabine
  Administered intravenously
• Drug: Lenalidomide
  Administered orally
• Drug: Rituximab
  Administered intravenously
• Drug: Doxorubicin
  Administered intravenously
• Drug: Vincristine
  Administered intravenously
• Drug: Prednisone
  Administered orally
• Drug: Bendamustine
  Administered intravenously

Study Arms

• Experimental: Axicabtagene Ciloleucel
  Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered.
  Interventions:

  • Biological: Axicabtagene Ciloleucel
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
• Active Comparator: Standard of Care Therapy

  Participants will receive the investigator's choice of one of the following therapies/dosing schedules:

  • Rituximab plus lenalidomide (R^2) for 12 cycles (28-day cycle)

    • Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m^2 on Day 1, Day 8, Day 15, and Day 22
    • Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1
    • Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21

  • Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle)

    • rituximab 375 mg/m^2 on Day 1
    • cyclophosphamide 750 mg/m^2 on Day 1
    • doxorubicin 50 mg/m^2 on Day 1
    • vincristine 1.4 mg/m^2 (maximum 2 mg) on Day 1
    • prednisone 40 mg/m^2 on Day 1 through Day 5

  • Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle)

    • rituximab 375 mg/m^2 on Day 1
    • bendamustine 90 mg/m^2 on Day 1 and Day 2
  Interventions:

  • Drug: Cyclophosphamide
  • Drug: Lenalidomide
  • Drug: Rituximab
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Bendamustine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 9, 2022): 230
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2030
• Estimated Primary Completion Date: October 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Medical Information; 844-454-5483(1-844-454-KITE); medinfo@kitepharma.com

• Listed Location Countries: France, Germany, Italy, Japan, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05371093
• Other Study ID Numbers: KT-US-473-0133; 2021-003260-28 ( Other Identifier: European Medicines Agency )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences ( Kite, A Gilead Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Kite, A Gilead Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Kite Study Director; Kite, A Gilead Company

• PRS Account: Gilead Sciences
• Verification Date: April 2024