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

NCT ID: NCT04314843

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-26
• Study Completion Date: 2022-07-27

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.

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.

Conditions

Relapsed/Refractory Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Administered according to package insert

Fludarabine

Intervention Type: DRUG

Administered according to package insert

Lenzilumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion

Axicabtagene Ciloleucel

Intervention Type: BIOLOGICAL

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

Interventions

Cyclophosphamide

Administered according to package insert

Intervention Type: DRUG

Fludarabine

Administered according to package insert

Intervention Type: DRUG

Lenzilumab

Administered as an IV infusion

Intervention Type: BIOLOGICAL

Axicabtagene Ciloleucel

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Humaneered® anti-human GM-CSF monoclonal antibody; Yescarta®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Humanigen, Inc.

INDUSTRY

Sponsor Role: collaborator

Kite, A Gilead Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

Stanford University

Palo Alto, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Northwestern University

Evanston, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Columbia University Medical Center, New York-Presbyterian Hospital

New York, New York, United States

Levine Cancer Center

Charlotte, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

Vanderbilt University

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: Translational Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=KT-US-471-0119

Gilead Clinical Trials Website

Other Identifiers

2019-004568-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KT-US-471-0119

Identifier Type: -

Identifier Source: org_study_id