- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04314843
Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma (ZUMA-19)
A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and Axicabtagene Ciloleucel in Subjects With Relapsed or Refractory Large B-cell Lymphoma (ZUMA-19)
The primary objectives of this study are:
Phase 1: To evaluate the safety of sequenced therapy with lenzilumab and axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma and identify the most appropriate dose of lenzilumab for Phase 2.
Phase 2: To evaluate the incidence of neurologic events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of lenzilumab in participants with relapsed or refractory large B-cell lymphoma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study was intended to be a Phase 1/2, but the planned Phase 2 part has been canceled.
All participants who received an infusion of lenzilumab and axicabtagene ciloleucel will be provided the opportunity to transition to a separate long-term follow-up (LTFU) study, KT-US-982-5968.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Palo Alto, California, United States, 94305
- Stanford University
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Illinois
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Evanston, Illinois, United States, 60208
- Northwestern University
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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New York, New York, United States, 10032
- Columbia University Medical Center, New York-Presbyterian Hospital
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Cancer Center
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
- Individuals with large B-cell lymphoma, including Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, Primary mediastinal large B-cell lymphoma (PMBCL), High-grade B-cell lymphoma (HGBL), and DLBCL arising from Follicular lymphoma (FL)
Individuals must have relapsed disease after 2 or more lines of systemic therapy, or chemorefractory disease defined as the following:
No response to first-line therapy, including the following:
- Progressive disease (PD) as best response to first therapy
- Stable disease (SD) as best response after ≥ 4 cycles of first-line therapy (eg, 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP)), with SD duration no longer than 6 months from the last dose of therapy
No response to ≥ 2 lines of therapy, including the following:
- PD as best response to most recent therapy
- SD as best response after ≥ 2 cycles of last line of therapy
Individuals must have received adequate prior therapy including at a minimum:
- Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
- An anthracycline-containing chemotherapy regimen
- At least 1 measurable lesion according to the International Working Group Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
- Magnetic resonance imaging of the brain showing no evidence of central nervous system (CNS) lymphoma
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Individuals with a known medical history of tuberculosis or a risk for tuberculosis exposure require negative tuberculosis testing by either tuberculin skin test or interferon gamma release assay.
Adequate bone marrow function as evidenced by:
- Absolute neutrophil count ≥ 1000/μL
- Platelets ≥ 75,000/μL
- Absolute lymphocyte count ≥ 100/μL
Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
- Creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min
- Serum alanine aminotransferase or aspartate aminotransferase ≤ 2.5 upper limit of normal
- Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's Syndrome
- Cardiac ejection fraction ≥ 50% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria:
- History of Richter's transformation of chronic lymphocytic leukemia
- Autologous stem cell transplant (SCT) within 6 weeks of planned axicabtagene ciloleucel infusion
- History of allogeneic stem cell transplantation
- Prior CD19 targeted therapy or prior CAR T cell therapy
- History of pulmonary alveolar proteinosis (PAP)
- History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg positive) or hepatitis C (HCV) (anti-HCV positive) infection. A history of hepatitis B or hepatitis C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- Individuals with detectable Cerebrospinal fluid (CSF) malignant cells, or brain metastases, or with a history of CNS lymphoma, CSF 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Lenzilumab and Axicabtagene Ciloleucel
Phase 1: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab and axicabtagene ciloleucel on Day 0 to determine a recommended Phase 2 dose (RP2D) of lenzilumab.
Phase 2: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab, at the RP2D, and axicabtagene ciloleucel on Day 0.
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Administered according to package insert
Administered according to package insert
Administered as an IV infusion
Other Names:
A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene
Time Frame: First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.
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A DLT was defined as the following sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusions:
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First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.
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Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration
Time Frame: Up to 28 days
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Up to 28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events
Time Frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
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Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
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Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events
Time Frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
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Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
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Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome
Time Frame: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events
Time Frame: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators
Time Frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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CR rate: percentage of participants with CR (CMR;CRR).
CMR: positron emission tomography(PET)5-point scale(5PS) scores of 1(no uptake above background), 2(uptake ≤ mediastinum), 3(uptake > mediastinum but ≤ liver) with/without a residual mass); no new sites; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow.
CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter (LDi) of a lesion; no extra lymphatic sites; absent non-measured lesion;organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.
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First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators
Time Frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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ORR: Percentage of participants with CR(CMR;CRR) or PR(partial metabolic response(PMR);partial radiologic response (PRR)).CMR:PET 5PS scores of 1,2,3 with/without a residual mass;no new sites;no evidence of FDG-avid disease in bone marrow.CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in LDi of a lesion;no extra lymphatic sites;absent non-measured lesion;organ enlargement regress to normal;no new sites;bone marrow normal by morphology.PMR:5PS scores of 4(uptake moderately higher than liver),or 5(uptake markedly higher than liver and/or new lesions),with reduced uptake compared to baseline and residual masses of any size;no new sites;residual update > update in normal bone marrow but reduced compared with baseline.PRR:≥ 50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites;absent/normal, regressed, but no increase of nonmeasured lesions;spleen regressed by > 50% in length beyond normal;no new sites.
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First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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Phase 1 and Phase 2: Duration of Response (DOR) in Participants Who Experience an Objective Response Per IWG Lugano Classification as Determined by Study Investigators
Time Frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause.
Objective response is defined in outcome measure (OM) 7.
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First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators
Time Frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause.
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First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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Phase 1 and Phase 2: Overall Survival (OS)
Time Frame: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
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First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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Phase 1 and Phase 2: Pharmacodynamics: Peak Serum Level of CXCL10, Granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-8, TNF Alpha, GM-CSF, and MCP-1
Time Frame: Baseline up to Week 4
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Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4.
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Baseline up to Week 4
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Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood
Time Frame: Baseline up to Month 3
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Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion.
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Baseline up to Month 3
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Kite Study Director, Kite, A Gilead Company
Publications and helpful links
General Publications
- Kenderian, S. S., Oluwole, O. O., Mccarthy, P. L., Reshef, R., Shiraz, P., Ahmed, O., Le Gall, J., Nahas, M., Tang, L. And Neelapu, S. S. Zuma-19: A Phase 1/2 Multicenter Study of Lenzilumab Use With Axicabtagene Ciloleucel (Axi-Cel) In Patients (Pts) With Relapsed Or Refractory Large B Cell Lymphoma (R/R Lbcl). Blood 136(Supplement 1): 6-7, (2020). Conference Proceedings.
- Olalekan O. Oluwole, MBBS, Saad S. Kenderian, MD, Parveen Shiraz, MD, Reem Karmali, MD, MSc, Ran Reshef, MD, MSc, Philip L. McCarthy, MD, Nilanjan Ghosh, MD, PhD, Aleksandr Lazaryan, MD, PhD, MPH, Simone Filosto, PhD, Soumya Poddar, PhD, Daqin Mao, PhD, Andrew Peng, MS, Adrian Kilcoyne, MD, MPH, Myrna Nahas, MD, Sattva S. Neelapu, MD. A Phase 1/2 Study of Axicabtagene Ciloleucel Plus Lenzilumab in Patients With Relapsed or Refractory Large B-Cell Lymphoma. American Society of Hemotology; Dec 10-13, 2022; New Orleans, LA. Abstract 4635
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Cyclophosphamide
- Fludarabine
- Axicabtagene ciloleucel
- Lenzilumab
Other Study ID Numbers
- KT-US-471-0119
- 2019-004568-23 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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