Clinical trial NCT05459571: Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma
Official title: A Phase 2 Open-Label, Multicenter Study Evaluating The Safety And Efficacy of Axicabtagene Ciloleucel Concomitant With Prophylactic Steroids In Subjects With Relapsed Or Refractory Large B-Cell Lymphoma In The Outpatient Setting
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed or Refractory Large B-cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2022-07-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.

Detailed description: Participants who complete at minimum 24 months follow up will be transitioned to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed large B-cell lymphoma (LBCL), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below:

  * Diffuse large B-cell lymphoma (DLBCL) not otherwise specified.
  * High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement.
  * DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL.
  * Primary mediastinal (thymic) LBCL.
  * Primary cutaneous DLBCL, leg type.
  * Transformation of follicular lymphoma to DLBCL will also be included.
* Relapsed or refractory disease after 1 or more lines of therapy.
* Individuals must have received adequate prior therapy including:

  * Anti-CD20 monoclonal antibody AND
  * An anthracycline-containing chemotherapy regimen.
* At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements.

Key Exclusion Criteria:

* History of autologous or allogeneic stem cell transplant.
* Prior cluster of differentiation (CD)19 targeted therapy.
* Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
* Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor.
* Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease.
* In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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

Primary outcomes:
measure: Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events
timeFrame: Up to 24 months
Secondary outcomes:
measure: Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
timeFrame: First infusion date of axicabtagene ciloleucel up to 24 months
measure: Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
timeFrame: First infusion date of axicabtagene ciloleucel up to 24 months
measure: Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours
timeFrame: First infusion date of axicabtagene ciloleucel up to 72 hours
measure: Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants 3 Days After Infusion Date
timeFrame: First infusion date of axicabtagene ciloleucel up to 3 days
measure: Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days
timeFrame: First infusion date of axicabtagene ciloleucel up to 7 days
measure: Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days
timeFrame: First infusion date of axicabtagene ciloleucel up to 14 days
measure: Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days
timeFrame: First infusion date of axicabtagene ciloleucel up to 30 days
measure: Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion
timeFrame: First infusion date of axicabtagene ciloleucel up to 24 months
measure: Proportion of Intensive Care Unit (ICU) Admitted Participants
timeFrame: Up to 24 months
measure: Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion
timeFrame: Up to 24 months
measure: Percentage of Participants Experiencing Treatment- Emergent Adverse Events
timeFrame: First infusion date of axicabtagene ciloleucel up to 24 months
measure: Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events
timeFrame: First infusion date of axicabtagene ciloleucel up to 24 months
measure: Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6
timeFrame: Baseline, 6 Months
measure: Objective Response Rate (ORR) as Assessed by Investigator Assessment
timeFrame: Up to 24 months
measure: Complete Response (CR) Rate as Assessed by Investigator Assessment
timeFrame: Up to 24 months
measure: Duration of response (DOR) as Assessed by Investigator Assessment
timeFrame: Up to 24 months
measure: Progression-free Survival (PFS) as Assessed by Investigator Assessment
timeFrame: Up to 24 months
measure: Event Free Survival (EFS) as Assessed by Investigator Assessment
timeFrame: Up to 24 months
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
timeFrame: Up to 24 months
measure: Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70
timeFrame: Up to 24 months
measure: Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin
timeFrame: Up to 24 months
measure: Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin
timeFrame: Up to 24 months
measure: Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1)
timeFrame: Up to 24 months
measure: Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials, LLC
state: Ohio
city: Greenville
country: United States
facility: Prisma Health - Upstate
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Healthcare
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: