Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma (ZUMA-19)

July 17, 2023 updated by: Kite, A Gilead Company

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

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

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Palo Alto, California, United States, 94305
        • Stanford University
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Illinois
      • Evanston, Illinois, United States, 60208
        • Northwestern University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10032
        • Columbia University Medical Center, New York-Presbyterian Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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.
Administered according to package insert
Administered according to package insert
Administered as an IV infusion
Other Names:
  • Humaneered® anti-human GM-CSF monoclonal antibody
A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.
Other Names:
  • Yescarta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.

A DLT was defined as the following sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusions:

  • Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer
  • Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer
  • Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy requiring intubation for airway protection
  • Any sequenced therapy-related Grade 5 event
First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.
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
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events
Time Frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events
Time Frame: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.
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.
Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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.
Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.
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).
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.
First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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).
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.
First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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).
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.
First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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).
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.
First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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).
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).
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
Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4.
Baseline up to Week 4
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
Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion.
Baseline up to Month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 26, 2020

Primary Completion (Actual)

March 16, 2021

Study Completion (Actual)

July 27, 2022

Study Registration Dates

First Submitted

March 17, 2020

First Submitted That Met QC Criteria

March 17, 2020

First Posted (Actual)

March 19, 2020

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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