Study of Brexucabtagene Autoleucel (KTE-X19) for the Treatment of Individuals With Relapsed/Refractory B-Cell Malignancies (ZUMA-18)

• ClinicalTrials.gov Identifier: NCT04162756
• Expanded Access Status: Approved for marketing
• First Posted: November 14, 2019
• Last Update Posted: October 14, 2021
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

Study Description

Brief Summary:

The primary objectives of this study are:

Cohort 1: to provide access to brexucabtagene autoleucel (KTE-X19) for individuals with relapsed or refractory (r/r) mantle cell lymphoma (MCL) until KTE-X19 is commercially available

Cohort 2: To provide access to KTE-X19 for individuals with r/r MCL whose commercially manufactured product did not meet commercial release specification(s)

Condition or disease	Intervention/treatment
Relapse/Refractory Mantle Cell Lymphoma	Biological: Brexucabtagene Autoleucel (KTE-X19); Drug: Fludarabine; Drug: Cyclophosphamide

Detailed Description:

This is an open-label, expanded access study of KTE-X19 for the treatment of individuals with r/r B-cell malignancies. The study will consist of 2 cohorts as indicated below:

Cohort 1 will enroll individuals prior to commercial availability of KTE-X19 for the proposed indication.

Cohort 2 will enroll individuals after KTE-X19 becomes commercially available in cases when KTE-X19 does not meet commercial release specification(s).

The participants who received an infusion of KTE-X19 will be provided the opportunity to transition to a separate long-term follow-up (LTFU) study, KT-US-982-5968.

Study Design

• Study Type: Expanded Access
• Expanded Access Type: Treatment IND/Protocol
• Official Title: A Multicenter, Open-label, Expanded Access Study of KTE-X19 for the Treatment of Subjects With Relapsed/Refractory B-Cell Malignancies

Interventions

Intervention Details:

• Biological: Brexucabtagene Autoleucel (KTE-X19)
  A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells/kg administered intravenously.
  Other Name: Tecartus™
• Drug: Fludarabine
  Administered per package insert
• Drug: Cyclophosphamide
  Administered per package insert

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All

Criteria

Key Inclusion Criteria:

Cohort 1:

• Pathologically confirmed mantel cell lymphoma (MCL), with documentation of either overexpression of cyclin D1 or presence of t(11;14)

• Received at least one prior regimen for MCL. Prior therapy must have included:

  • Anthracycline or bendamustine-containing chemotherapy, or
  • Anti-CD20 monoclonal antibody therapy, or
  • Treatment with Bruton's tyrosine kinase inhibitor (BTKi): ibrutinib, acalabrutinib, or a BTKi in a clinical trial for r/r MCL.

• Relapsed or refractory disease, defined by the following:

  • Disease progression after last regimen, or
  • Failure to achieve a partial response (PR) or complete response (CR) to the last regimen
• Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) ≥ 1,000/uL
• Platelet count ≥ 75,000/uL
• Absolute lymphocyte count ≥ 100/uL

• Adequate renal, hepatic, pulmonary, and cardiac function defined as the following:

  • Creatinine clearance (as estimated by Cockcroft Gault formula) ≥ 60 cc/min
  • Serum alanine aminotransferase/aspartate aminotransferase (ALT)/AST) ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dl, except in individuals with Gilbert's syndrome
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion (except trace or physiological) as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
  • No clinically significant pleural effusion
  • Baseline oxygen saturation > 92% on room air
• Females of childbearing potential must have a negative serum or urine pregnancy test. Females who have undergone surgical sterilization or who have been post-menopausal for at least 2 years are not considered to be of childbearing potential.
• At least 1 measurable lesion. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. If the only measurable disease is lymph node disease, at least 1 lymph node should be ≥ 2 cm.

Cohort 2:

• Individuals whose commercial manufacture of KTE-X19 did not meet commercial release specification(s)

Key Exclusion Criteria:

Cohort 1:

• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or hepatitis C infection.
• History of detectable cerebrospinal fluid (CSF) malignant cells or brain metastases or with a history of CNS lymphoma, CSF malignant cells, or brain metastases
• History of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement

Cohort 2:

• Any medical condition that, as deemed by the treating physician, may interfere with assessment of safety or efficacy of study treatment

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, California

Stanford Cancer Institute

Stanford, California, United States, 94305

United States, Colorado

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, New Jersey

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States, 37232

United States, Texas

The University of TX MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Kite, A Gilead Company

Investigators

• Study Director: Kite Study Director; Kite, A Gilead Company

More Information

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT04162756
• Other Study ID Numbers: KT-US-472-0118
• First Posted: November 14, 2019
• Last Update Posted: October 14, 2021
• Last Verified: October 2021

Additional relevant MeSH terms:

Lymphoma, Mantle-Cell; Neoplasms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Fludarabine; Brexucabtagene autoleucel; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological