Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma

NCT02348216 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: KTE-C19-1012015-005007-86
• Study Type: interventional
• Target: 307
• Locations: 6 countries
• Sites: 36

Brief Summary

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6). The primary objectives of this study are:

• Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens
• Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel
• Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities Subjects who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.

Conditions

Refractory Diffuse Large B Cell Lymphoma (DLBCL); Relapsed Diffuse Large B-Cell Lymphoma; Transformed Follicular Lymphoma (TFL); Primary Mediastinal B-cell Lymphoma (PMBCL); High Grade B-cell Lymphoma (HGBCL)

Outcome Measures

Primary Outcomes (6)

• Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)

  DLT was defined as axicabtagene ciloleucel-related events with onset within first 30 days following infusion: * Grade (GR) 4 neutropenia lasting \> 21 days and GR 4 thrombocytopenia lasting \> 35 days from day of cell transfer; * Any axicabtagene ciloleucel-related AE requiring intubation; * All other GR 3 toxicities lasting \> 3 days and all GR 4 toxicities, with exception of following conditions which were not considered DLTs: aphasia/dysphasia or confusion/cognitive disturbance which resolved to GR ≤ 1 within 2 weeks and to baseline within 4 weeks; fever GR 3; myelosuppression defined as lymphopenia, decreased hemoglobin, neutropenia and thrombocytopenia unless neutropenia and thrombocytopenia met DLT definition described above; immediate hypersensitivity reactions occurring within 2 hours of cell infusion that were reversible to a ≤ GR 2 within 24 hours of cell administration with standard therapy; hypogammaglobulinemia GR 3 or 4.

  First infusion date of axicabtagene ciloleucel up to 30 days

• Phase 2 Pivotal Study (Cohorts 1 and 2): Overall Response Rate (ORR) as Assessed by Investigator Per Revised International Working Group (IWG) Response Criteria for Malignant Lymphoma

  ORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR), as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease; multiple splenic and hepatic nodules (if present) must regress by ≥ 50% in the SPD; \> 50% decrease in the greatest transverse diameter for single nodules. 95% confidence interval (CI) was calculated by Clopper-Pearson method.

  First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 7.7 years)

• Phase 2 Safety Management Study (Cohort 3): Percentage of Participants With Treatment-Emergent Cytokine Release Syndrome (CRS) and Neurologic Toxicities by Severity Grades

  TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or continuous venovenous hemodialysis (CVVHD), and Grade 5: Death. Neurologic toxicities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.

  First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 6.8 years)

• Phase 2 Safety Management Study (Cohort 4): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

  TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.

  First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 5.4 years)

• Phase 2 Safety Management Study (Cohort 5): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

  TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.

  First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.4 years)

• Phase 2 Safety Management Study (Cohort 6): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

  TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.

  First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.1 years)

Secondary Outcomes (22)

• Phase 2: Duration of Response (DOR) as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma

  First OR to last follow-up visit (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)

• Phase 1 Study: ORR as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma

  First infusion date of axicabtagene ciloleucel to the data cutoff date of 27 January 2017 (maximum: 20 months)

• Phase 2 Pivotal Study (Cohorts 1 and 2): ORR Per Independent Radiological Review Committee (IRRC)

  First infusion date of axicabtagene ciloleucel to the data cutoff date of 11 August 2018 (maximum: 2.7 years)

• Phase 2 Safety Management Study (Cohorts 3, 4, 5, and 6): ORR as Assessed by Investigator Per the Revised IWG Response Criteria for Malignant Lymphoma

  First infusion date of axicabtagene ciloleucel to last follow-up visit (maximum duration: 6.8, 5.4, 4.4, 4.1 years for Cohorts 3, 4, 5, and 6 respectively)

• Phase 2: Progression-Free Survival (PFS) as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma

  First infusion date of axicabtagene ciloleucel to disease progression or death regardless of cause (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)

Study Arms (7)

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy

EXPERIMENTAL

Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 intravenously \[IV\] over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Phase 2 (Pivotal Study): Cohort 1

EXPERIMENTAL

Participants with refractory DLBCL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Phase 2 (Pivotal Study): Cohort 2

EXPERIMENTAL

Participants with refractory PMBCL or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Phase 2 (Safety Management Study): Cohort 3

EXPERIMENTAL

Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Levetiracetam; Drug: Tocilizumab

Phase 2 (Safety Management Study): Cohort 4

EXPERIMENTAL

Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m\^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants will receive tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Levetiracetam; Drug: Tocilizumab; Drug: Dexamethasone; Drug: High-dose methylprednisolone; Drug: Bendamustine; Drug: Rituximab

Phase 2 (Safety Management Study): Cohort 5

EXPERIMENTAL

Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy will receive debulking therapy (R-CHOP:rituximab 375mg/m\^2 D1,doxorubicin 50mg/m\^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m\^2 D1,vincristine 1.4 mg/m\^2 D1 or R-ICE:rituximab 375mg/ m\^2 D1,ifosfamide 5g/m\^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m\^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m\^2 D1,gemcitabine 1000mg/m\^2 D2,oxaliplatin 100mg/m\^2 D2 or R-GDP:rituximab 375mg/m\^2 D1 or D8,gemcitabine 1g/m\^2 D1 \& D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m\^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Levetiracetam; Drug: Rituximab; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Cisplatin

Phase 2 (Safety Management Study): Cohort 6

EXPERIMENTAL

Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m\^2 HDMP for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants will receive tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Levetiracetam; Drug: Tocilizumab; Drug: Dexamethasone; Drug: High-dose methylprednisolone; Drug: Bendamustine; Drug: Rituximab; Drug: Methylprednisolone

Interventions

Axicabtagene Ciloleucel BIOLOGICAL

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg.

Also known as: Yescarta®

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy; Phase 2 (Pivotal Study): Cohort 1; Phase 2 (Pivotal Study): Cohort 2; Phase 2 (Safety Management Study): Cohort 3; Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 5; Phase 2 (Safety Management Study): Cohort 6

Fludarabine DRUG

Administered according to package insert

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy; Phase 2 (Pivotal Study): Cohort 1; Phase 2 (Pivotal Study): Cohort 2; Phase 2 (Safety Management Study): Cohort 3; Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 5; Phase 2 (Safety Management Study): Cohort 6

Cyclophosphamide DRUG

Administered according to package insert

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy; Phase 2 (Pivotal Study): Cohort 1; Phase 2 (Pivotal Study): Cohort 2; Phase 2 (Safety Management Study): Cohort 3; Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 5; Phase 2 (Safety Management Study): Cohort 6

Levetiracetam DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 3; Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 5; Phase 2 (Safety Management Study): Cohort 6

Tocilizumab DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 3; Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 6

Dexamethasone DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 6

High-dose methylprednisolone DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 6

Bendamustine DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 6

Rituximab DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 4; Phase 2 (Safety Management Study): Cohort 5; Phase 2 (Safety Management Study): Cohort 6

Doxorubicin DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Prednisone DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Vincristine DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Ifosfamide DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Carboplatin DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Etoposide DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Gemcitabine DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Oxaliplatin DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Cisplatin DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 5

Methylprednisolone DRUG

Administered according to package insert

Phase 2 (Safety Management Study): Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed:
• Diffuse Large B Cell Lymphoma (DLBCL)
• Primary Mediastinal Large B Cell Lymphoma (PMBCL)
• Transformation Follicular Lymphoma (TFL)
• High grade B-cell lymphoma (HGBCL)
• Chemotherapy-refractory disease, defined as one of more of the following:
• No response to last line of therapy i. Progressive disease (PD) as best response to most recent therapy regimen ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
• Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
• Individuals must have received adequate prior therapy including at a minimum:
• Anti-cluster of differentiate 20 (CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative and
• an anthracycline containing chemotherapy regimen
• for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
• At least one measurable lesion per revised international working group (IWG Response Criteria
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) ≥ 1000/microliters (uL)

You may not qualify if:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
• History of allogeneic stem cell transplantation
• Prior chimeric antigen receptor (CAR) 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 (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
• History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
• Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
• History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (36)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope

Duarte, California, 91010-3012, United States

Location

University of California San Diego (UCSD)

La Jolla, California, 92093-0820, United States

Location

Stanford University

Palo Alto, California, 94305, United States

Location

University of California Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

Sarah Cannon - Denver

Denver, Colorado, 80218, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198-7680, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Sarah Cannon - Tennesee

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

Location

Sarah Cannon-Methodist Healthcare System - San Antonio

San Antonio, Texas, 78229, United States

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Saint Louis

Paris, 75475, France

Location

Hopital Haut-Leveque

Pessac, 44035, France

Location

CHU de Rennes

Rennes, 35033, France

Location

Universitätsklinik Dresden

Dresden, 01307, Germany

Location

University Hospital of Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Tel Aviv Souraski Medical Center

Tel Aviv, 64239, Israel

Location

Academisch Medisch Centrum

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (20)

• Topp MS, van Meerten T, Wermke M et al. Preliminary Results of Earlier Steroid Use with Axicabtagene Ciloleucel in Patients With Relapsed/Refractory Large B Cell Lymphoma. Poster presented at the American Society of Presented at: American Society of Clinical Oncology Annual Meeting. May 31-June 4, 2019; Chicago, Illinois; Abstract 7558.

  RESULT

• Topp, M, van Meerten T, Houot R, et al. (2019). Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 243. Abstract 626.

  RESULT

• Abstract: Oluwole OO, et al. Prophylactic corticosteroid use with axicabtagene ciloleucel in patients with relapsed/refractory large B-cell lymphoma. Transplantation and Cellular Therapy 2021.

  RESULT

• Oluwole OO, Bouabdallah K, Munoz J, De Guibert S, Vose JM, Bartlett NL, Lin Y, Deol A, McSweeney PA, Goy AH, Kersten MJ, Jacobson CA, Farooq U, Minnema MC, Thieblemont C, Timmerman JM, Stiff P, Avivi I, Tzachanis D, Kim JJ, Bashir Z, McLeroy J, Zheng Y, Rossi JM, Johnson L, Goyal L, van Meerten T. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021 Aug;194(4):690-700. doi: 10.1111/bjh.17527. Epub 2021 Jul 22.

  PMID: 34296427 RESULT

• Santa Monica, Calif. New Four-Year Data Show Long-Term Survival in Patients With Large B-Cell Lymphoma Treated With Yescarta® in ZUMA-1 Trial. Data presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. December 5, 2020; Abstract 1187

  RESULT

• Max S. Topp, Tom van Meerten, Martin Wermke, Pieternella J. Lugtenburg, Monique C. Minnema, Kevin W. Song, Catherine Thieblemont, Yizhou Jiang, Vicki Plaks, Anne Kerber, Marie José Kersten. Preliminary Results of Earlier Steroid Use With Axicabtagene Ciloleucel in Patients With Relapsed/ Refractory Large B Cell Lymphoma. Poster presented at ASCO 2019 Annual Meeting. June 3, 2019; Abstract 7558

  RESULT

• Sattva S. Neelapu, Caron A. Jacobson, Olalekan O. Oluwole, Javier Munoz, Abhinav Deol, David B. Miklos, Nancy L. Bartlett, Ira Braunschweig, Yizhou Jiang, Jenny J. Kim, Lianqing Zheng, John M. Rossi, Frederick L. Locke. Axicabtagene Ciloleucel (Axi-Cel) In Refractory Large B Cell Lymphoma: Outcomes in Patients ≥ or < 65 Years of Age in the Pivotal Phase 1/2 ZUMA-1 Study. Poster presented at EHA 2019. June 15, 2019; Abstract 1066

  RESULT

• Max S. Topp, Tom van Meerten, Martin Wermke, Pieternella J. Lugtenburg, Monique C. Minnema, Kevin W. Song, Catherine Thieblemont, Yizhou Jiang, Vicki Plaks, Anne Kerber, Marie José Kersten. Axicabtagene Ciloleucel (Axi-Cel) in Patients With Relapsed/Refractory Large B Cell Lymphoma: Preliminary Results of Earlier Steroid Use. Poster presented at EHA 2019. June 15, 2019; Abstract 1067

  RESULT

• Sattva S. Neelapu, John M. Rossi, Caron A. Jacobson, Frederick L. Locke, David B. Miklos, Patrick M. Reagan, Scott Rodig, Lazaros J. Lekakis, Ian W. Flinn, Lianqing Zheng, Francesca Milletti, Edmund Chang, Allen Xue, Vicki Plaks, Jenny J. Kim, Adrian Bot. CD19-Loss With Preservation of Other B Cell Lineage Features in Patients With Large B Cell Lymphoma Who Relapsed Post-Axi-Cel. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 203. Abstract 704.

  RESULT

• Sattva S. Neelapu, Frederick L. Locke, Nancy L. Bartlett, Lazaros J. Lekakis, Patrick Reagan, David B. Miklos, Caron A. Jacobson, Ira Braunschweig, Olalekan Oluwole, Tanya Siddiqi, Yi Lin, Michael Crump, John Kuruvilla, Eric Van Den Neste, Umar Farooq, Lynn Navale, Venita DePuy, Jenny J. Kim, Christian Gisselbrecht. A Comparison of Two-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 4095. Abstract 626.

  RESULT

• Chartier M, Filosto S, Peyret T, Chiney M, Milletti F, Budka J, Ndi A, Dong J, Vardhanabhuti S, Mao D, Duffull S, Dodds M, Shen R. Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma. Clin Pharmacokinet. 2024 Sep;63(9):1283-1299. doi: 10.1007/s40262-024-01413-z. Epub 2024 Sep 6.

  PMID: 39240498 DERIVED

• Locke FL, Siddiqi T, Jacobson CA, Ghobadi A, Ahmed S, Miklos DB, Perales MA, Munoz J, Fingrut WB, Pennisi M, Gauthier J, Shadman M, Gowda L, Mirza AS, Abid MB, Hong S, Majhail NS, Kharfan-Dabaja MA, Khurana A, Badar T, Lin Y, Bennani NN, Herr MM, Hu ZH, Wang HL, Baer A, Baro E, Miao H, Spooner C, Xu H, Pasquini MC. Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity. Blood. 2024 Jun 27;143(26):2722-2734. doi: 10.1182/blood.2023023447.

  PMID: 38635762 DERIVED

• Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. doi: 10.1182/blood.2022018893.

  PMID: 36821768 DERIVED

• 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.

  PMID: 34515338 DERIVED

• Maloney DG, Kuruvilla J, Liu FF, Kostic A, Kim Y, Bonner A, Zhang Y, Fox CP, Cartron G. Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. J Hematol Oncol. 2021 Sep 8;14(1):140. doi: 10.1186/s13045-021-01144-9.

  PMID: 34493319 DERIVED

• Westin JR, Kersten MJ, Salles G, Abramson JS, Schuster SJ, Locke FL, Andreadis C. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021 Oct 1;96(10):1295-1312. doi: 10.1002/ajh.26301. Epub 2021 Aug 13.

  PMID: 34310745 DERIVED

• Upadhyay R, Boiarsky JA, Pantsulaia G, Svensson-Arvelund J, Lin MJ, Wroblewska A, Bhalla S, Scholler N, Bot A, Rossi JM, Sadek N, Parekh S, Lagana A, Baccarini A, Merad M, Brown BD, Brody JD. A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy. Cancer Discov. 2021 Mar;11(3):599-613. doi: 10.1158/2159-8290.CD-20-0756. Epub 2020 Dec 17.

  PMID: 33334730 DERIVED

• Locke FL, Rossi JM, Neelapu SS, Jacobson CA, Miklos DB, Ghobadi A, Oluwole OO, Reagan PM, Lekakis LJ, Lin Y, Sherman M, Better M, Go WY, Wiezorek JS, Xue A, Bot A. Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Oct 13;4(19):4898-4911. doi: 10.1182/bloodadvances.2020002394.

  PMID: 33035333 DERIVED

• Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. doi: 10.1016/S1470-2045(18)30864-7. Epub 2018 Dec 2.

  PMID: 30518502 DERIVED

• Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.

  PMID: 29226797 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

axicabtagene ciloleucel; fludarabine; Cyclophosphamide; Levetiracetam; tocilizumab; Dexamethasone; Methylprednisolone; Bendamustine Hydrochloride; Rituximab; Doxorubicin; Prednisone; Vincristine; Ifosfamide; Carboplatin; Etoposide; Gemcitabine; Oxaliplatin; Cisplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Acetamides; Amides; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Prednisolone; Butyrates; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Oxazines; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: January 28, 2015
• Study Start: April 21, 2015
• Primary Completion: July 27, 2023
• Study Completion: July 27, 2023
• Last Updated: June 4, 2024
• Results First Posted: November 23, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (23); IL (1); NL (4); CA (2); FR (3); DE (3)