Study Details

PROTOCOL 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.

Participation Requirements

Age

18 Years +

Sex

All

Healthy Volunteers

Medical Condition

Relapsed/Refractory Large B-cell Lymphoma

Gender

N/A

Date

May 2020 - March 2021

Study Type

Interventional

Study Phase

Phase 1

Product

Cyclophosphamide, Fludarabine, Lenzilumab, Axicabtagene Ciloleucel

Eligibility Information

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

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.

Locations

Locations (10)

Stanford University

Palo Alto, California, United States, 94305

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Northwestern University

Evanston, Illinois, United States, 60208

Mayo Clinic

Rochester, Minnesota, United States, 55905

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

Levine Cancer Center

Charlotte, North Carolina, United States, 28204

Oregon Health & Science University

Portland, Oregon, United States, 97239

Vanderbilt University

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Houston, Texas, United States, 77030

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

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