Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma (ZUMA-19)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04314843|
Recruitment Status : Terminated (Development program terminated.)
First Posted : March 19, 2020
Last Update Posted : August 30, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
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.
|Condition or disease||Intervention/treatment||Phase|
|Relapsed/Refractory Large B-cell Lymphoma||Drug: Cyclophosphamide Drug: Fludarabine Biological: Lenzilumab Biological: Axicabtagene Ciloleucel||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||May 26, 2020|
|Actual Primary Completion Date :||March 16, 2021|
|Actual Study Completion Date :||July 27, 2022|
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 Name: Humaneered® anti-human GM-CSF monoclonal antibody
Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.
Other Name: Yescarta®
- For Phase 1: Percentage of Participants Experiencing Adverse Events Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy with Lenzilumab and Axicabtagene [ Time Frame: Up to 28 days ]Dose-limiting toxicity is defined as protocol-defined sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusion.
- For 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 ]
- For Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 12 months ]
- For Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events [ Time Frame: Up to 24 months ]
- For Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome [ Time Frame: Up to 24 months ]
- For Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events [ Time Frame: Up to 24 months ]
- For Phase 1 and Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]ORR is defined as the incidence of either a Complete Response (CR) or a Partial Response (PR) per the International Working Group (IWG) Lugano Classification as determined by the study investigators.
- For Phase 1 and Phase 2: Complete Response (CR) Rate [ Time Frame: Up to 2 years ]CR rate is defined as the incidence of CR per the IWG Lugano Classification as determined by the study investigators
- For Phase 1 and Phase 2: Duration of Response (DOR) in Participants who Experience an Objective Response [ Time Frame: Up to 2 years ]Among participants who experience an objective response, DOR is defined as the date of participants' first objective response to disease progression per the IWG Lugano Classification as determined by study investigators or death from any cause.
- For Phase 1 and Phase 2: Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the IWG Lugano Classification as determined by study investigators or death from any cause.
- For Phase 1 and Phase 2: Overall Survival (OS) [ Time Frame: Up to 2 years ]OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
- For Phase 1 and Phase 2: Pharmacodynamics: Levels of Cytokines in Blood [ Time Frame: Up to 3 months ]
- For Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Levels of anti-CD19 CAR T Cells in Blood [ Time Frame: Up to 12 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04314843
|United States, California|
|Palo Alto, California, United States, 94305|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|Evanston, Illinois, United States, 60208|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Columbia University Medical Center, New York-Presbyterian Hospital|
|New York, New York, United States, 10032|
|United States, North Carolina|
|Levine Cancer Center|
|Charlotte, North Carolina, United States, 28204|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Director:||Kite Study Director||Kite, A Gilead Company|
|Responsible Party:||Kite, A Gilead Company|
|Other Study ID Numbers:||
2019-004568-23 ( EudraCT Number )
|First Posted:||March 19, 2020 Key Record Dates|
|Last Update Posted:||August 30, 2022|
|Last Verified:||August 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|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/|
Statistical Analysis Plan (SAP)
|Time Frame:||18 months after study completion|
|Access Criteria:||A secured external environment with username, password, and RSA code.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
Chimeric Antigen Receptor (CAR)
Neoplasms by Histologic Type
Immune System Diseases
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological