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

NCT04314843 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: KT-US-471-01192019-004568-23
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 10

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.

Conditions

Relapsed/Refractory Large B-cell Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase 1: Percentage of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Related to Sequenced Therapy With Lenzilumab and Axicabtagene

  A DLT was defined as the following sequenced therapy-related events with onset within the first 28 days following lenzilumab and axicabtagene ciloleucel infusions: * Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer * Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer * Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy requiring intubation for airway protection * Any sequenced therapy-related Grade 5 event

  First infusion of lenzilumab and axicabtagene ciloleucel up to 28 days.

• Phase 2: Percentage of Participants Experiencing Grade 2 or Higher Neurologic Events Within 28 Days of Axicabtagene Ciloleucel Administration

  Up to 28 days

Secondary Outcomes (11)

• Phase 1 and Phase 2: Percentage of Participants Experiencing Adverse Events

  Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

• Phase 1 and Phase 2: Percentage of Participants Experiencing Serious Adverse Events

  Enrollment through 3 months after lenzilumab and axicabtagene ciloleucel infusion.

• Phase 1 and Phase 2: Percentage of Participants Experiencing Cytokine Release Syndrome

  Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

• Phase 1 and Phase 2: Percentage of Participants Experiencing Neurologic Events

  Enrollment through 12 months after lenzilumab and axicabtagene ciloleucel infusion or until disease progression, whichever occurred first.

• Phase 1 and Phase 2: Complete Response (CR) Rate Per Internal Working Group (IWG) Lugano Classification as Determined by the Study Investigators

  First infusion date axicabtagene ciloleucel to data cut off date of 09 May 2022 (maximum duration: 22.3 months).

Study Arms (1)

Lenzilumab and Axicabtagene Ciloleucel

EXPERIMENTAL

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; Drug: Fludarabine; Biological: Lenzilumab; Biological: Axicabtagene Ciloleucel

Interventions

Cyclophosphamide DRUG

Administered according to package insert

Lenzilumab and Axicabtagene Ciloleucel

Fludarabine DRUG

Administered according to package insert

Lenzilumab and Axicabtagene Ciloleucel

Lenzilumab BIOLOGICAL

Administered as an IV infusion

Also known as: Humaneered® anti-human GM-CSF monoclonal antibody

Lenzilumab and Axicabtagene Ciloleucel

Axicabtagene Ciloleucel BIOLOGICAL

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

Also known as: Yescarta®

Lenzilumab and Axicabtagene Ciloleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead
• Humanigen, Inc.: collaborator

Study Sites (10)

Stanford University

Palo Alto, California, 94305, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center, New York-Presbyterian Hospital

New York, New York, 10032, United States

Location

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  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

  BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Recurrence

Interventions

Cyclophosphamide; fludarabine; lenzilumab; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 19, 2020
• Study Start: May 26, 2020
• Primary Completion: March 16, 2021
• Study Completion: July 27, 2022
• Last Updated: March 4, 2024
• Results First Posted: March 4, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (10)