Clinical Trials /

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

NCT04314843

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: KT-US-471-0119
  • SECONDARY ID: 2019-004568-23
  • NCT ID: NCT04314843

Conditions

  • Relapsed/Refractory Large B-cell Lymphoma

Interventions

DrugSynonymsArms
CyclophosphamideLenzilumab and Axicabtagene Ciloleucel
FludarabineLenzilumab and Axicabtagene Ciloleucel
LenzilumabHumaneered® anti-human GM-CSF monoclonal antibodyLenzilumab and Axicabtagene Ciloleucel
Axicabtagene CiloleucelYescarta®Lenzilumab and Axicabtagene Ciloleucel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Cyclophosphamide
  • Fludarabine
  • Lenzilumab
  • Axicabtagene Ciloleucel

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:For Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:For Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:For Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:For Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:For Phase 1 and Phase 2: Objective Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:For Phase 1 and Phase 2: Complete Response (CR) Rate
Time Frame:Up to 2 years
Safety Issue:
Description:CR rate is defined as the incidence of CR per the IWG Lugano Classification as determined by the study investigators
Measure:For Phase 1 and Phase 2: Duration of Response (DOR) in Participants who Experience an Objective Response
Time Frame:Up to 15 years
Safety Issue:
Description: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.
Measure:For Phase 1 and Phase 2: Progression-Free Survival (PFS)
Time Frame:Up to 15 years
Safety Issue:
Description: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.
Measure:For Phase 1 and Phase 2: Overall Survival (OS)
Time Frame:Up to 15 years
Safety Issue:
Description:OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Measure:For Phase 1 and Phase 2: Pharmacodynamics: Levels of Cytokines in Blood
Time Frame:Up to 3 months
Safety Issue:
Description:
Measure:For Phase 1 and Phase 2: Axicabtagene Ciloleucel Pharmacokinetics: Levels of anti-CD19 CAR T Cells in Blood
Time Frame:Up to 12 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kite, A Gilead Company

Trial Keywords

  • Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
  • GM-CSF antibody
  • Chimeric Antigen Receptor (CAR)
  • CD19

Last Updated

April 28, 2020