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

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ClinicalTrials.gov Identifier: NCT04314843
Recruitment Status : Recruiting
First Posted : March 19, 2020
Last Update Posted : September 16, 2020
Sponsor:
Collaborator:
Humanigen, Inc.
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Brief 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.

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 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2037

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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.

Drug: Cyclophosphamide
Administered according to package insert

Drug: Fludarabine
Administered according to package insert

Biological: Lenzilumab
Administered as an intravenous (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®




Primary Outcome Measures :
  1. 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.

  2. 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 ]

Secondary Outcome Measures :
  1. For Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events [ Time Frame: Up to 12 months ]
  2. For Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events [ Time Frame: Up to 24 months ]
  3. For Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome [ Time Frame: Up to 24 months ]
  4. For Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events [ Time Frame: Up to 24 months ]
  5. 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.

  6. 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

  7. For Phase 1 and Phase 2: Duration of Response (DOR) in Participants who Experience an Objective Response [ Time Frame: Up to 15 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.

  8. For Phase 1 and Phase 2: Progression-Free Survival (PFS) [ Time Frame: Up to 15 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.

  9. For Phase 1 and Phase 2: Overall Survival (OS) [ Time Frame: Up to 15 years ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

  10. For Phase 1 and Phase 2: Pharmacodynamics: Levels of Cytokines in Blood [ Time Frame: Up to 3 months ]
  11. For Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Levels of anti-CD19 CAR T Cells in Blood [ Time Frame: Up to 12 months ]


Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

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


Contacts
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Contact: Medical Information 844-454-5483(1-844-454-KITE) medinfo@kitepharma.com

Locations
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United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94305
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Columbia University Medical Center, New York-Presbyterian Hospital Recruiting
New York, New York, United States, 10032
United States, North Carolina
Levine Cancer Center Recruiting
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Kite, A Gilead Company
Humanigen, Inc.
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company
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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT04314843    
Other Study ID Numbers: KT-US-471-0119
2019-004568-23 ( EudraCT Number )
First Posted: March 19, 2020    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences ( Kite, A Gilead Company ):
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
GM-CSF antibody
Chimeric Antigen Receptor (CAR)
CD19
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists