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Relapsed/Refractory Large B-cell LymphomaPhase 1ZUMA-19NCT04314843

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

A Phase 1 study testing Cyclophosphamide, Fludarabine and Lenzilumab in people with Relapsed/Refractory Large B-cell Lymphoma, run by Kite, A Gilead Company at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Fludarabine and Lenzilumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
10 sitesUnited States
Study dates
26 May 2020to 27 Jul 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 26Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Levine Cancer Center

    Charlotte, North Carolina, 28204

  • Northwestern University

    Evanston, Illinois, 60208

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Columbia University Medical Center, New York-Presbyterian Hospital

    New York, New York, 10032

  • Stanford University

    Palo Alto, California, 94305

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Cyclophosphamide, Fludarabine, Lenzilumab, Axicabtagene Ciloleucel
Keywords
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), GM-CSF antibody, Chimeric Antigen Receptor (CAR), CD19
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Administered according to package insert

  • FludarabineDrug

    Administered according to package insert

  • LenzilumabBiological

    Also called Humaneered® anti-human GM-CSF monoclonal antibody

    Administered as an IV infusion

  • Axicabtagene CiloleucelBiological

    Also called Yescarta®

    A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.

Study groups in NCT04314843
Study groupRoleWhat they receive
Lenzilumab and Axicabtagene CiloleucelExperimentalPhase 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Lenzilumab; Biological: Axicabtagene Ciloleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene

    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

    Measured: First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.

  2. Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration

    Measured: Up to 28 days

Secondary outcomes (11)

  1. Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events

    Measured: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

  2. Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events

    Measured: Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

  3. Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome

    Measured: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

  4. Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events

    Measured: Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

  5. Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators

    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.

    Measured: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

  6. Phase 1 and Phase 2: Objective Response Rate (ORR) Per IWG Lugano Classification as Determined by Study Investigators

    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.

    Measured: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

  7. 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

    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.

    Measured: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

  8. Phase 1 and Phase 2: Progression-Free Survival (PFS) Per IWG Lugano Classification as Determined by Study Investigators

    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.

    Measured: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

  9. Phase 1 and Phase 2: Overall Survival (OS)

    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

    Measured: First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

  10. 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

    Peak is defined as the maximum post-baseline level of the analyte from baseline to Week 4.

    Measured: Baseline up to Week 4

  11. Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood

    Peak is defined as the maximum number of CAR T cells in blood measured after the axicabtagene ciloleucel infusion.

    Measured: Baseline up to Month 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2020
  2. Study start26 May 2020
  3. Primary completion16 Mar 2021
  4. Study completion27 Jul 2022

Why it stopped: Development program terminated and the decision was not due to any safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04314843
Sponsor's protocol ID
KT-US-471-0119
Other IDs
2019-004568-23, 2019
Acronym
ZUMA-19
Status last verified
Jul 2023
First submitted
17 Mar 2020
Last updated
4 Mar 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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/

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Lenzilumab in people with Relapsed/Refractory Large B-cell Lymphoma, run by Kite, A Gilead Company at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04314843, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2024.

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