Clinical trial NCT04002401: Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma
Official title: A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Large B-cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-06-28
Enrollment: 27
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 primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

Detailed description: Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed large B-cell lymphoma
* Chemotherapy-refractory disease, defined as one or more of the following:

  * No response to first-line therapy (primary refractory disease)
  * No response to second or greater lines of therapy OR
  * Refractory after autologous stem cell transplant (ASCT)
* At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).
* Individuals must have received adequate prior therapy, including at a minimum:

  * Anti-CD20 monoclonal antibody
  * An anthracycline-containing chemotherapy regimen
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

* Known CD19 negative or CD20 negative tumor
* History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
* Prior CAR therapy or other genetically modified T-cell therapy
* Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
* Prior CD19 targeted therapy
* Clinically significant infection or cardiopulmonary disease
* Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
* History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
* History of autoimmune disease
* History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

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

Primary outcomes:
measure: Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators
timeFrame: First infusion date up to maximum duration of 32.7 months
Secondary outcomes:
measure: Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
timeFrame: First infusion date up to maximum duration of 27 months
measure: Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value
timeFrame: First infusion date up to maximum duration of 27 months
measure: Objective Response Rate (ORR) Per the IWG Lugano Classification as Determined by Study Investigators
timeFrame: First infusion date up to maximum duration of 32.7 months
measure: Duration of Response (DOR) Per the IWG Lugano Classification as Determined by Study Investigators
timeFrame: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 32.7 months)
measure: Progression-Free Survival (PFS) Per the IWG Lugano Classification as Determined by Study Investigators
timeFrame: First infusion date up to disease progression or death regardless of cause (up to approximately 32.7 months)
measure: Overall Survival (OS)
timeFrame: First infusion date up to death regardless of cause (up to approximately 32.7 months)
measure: Peak Level of Anti-CD19 CAR T Cells in Blood
timeFrame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24
measure: Level of Anti-CD19 CAR T Cells in Blood by Visit
timeFrame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24
measure: Area Under the Curve of CAR T Cells From Day 0 to Day 28 (AUC0-28)
timeFrame: Baseline (Day 0), post-infusion on Days 7, 14, 21, and 28
measure: Time to Peak Level of Anti-CD19 CAR T Cells in Blood
timeFrame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center, New York Presbyterian Hospital
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References:
citation: Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.