Study Evaluating Brexucabtagene Autoleucel (KTE-X19) in Pediatric and Adolescent Participants With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia or Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

NCT02625480 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: KTE-C19-1042023-509440-97
• Study Type: interventional
• Target: 95
• Locations: 11 countries
• Sites: 30

Brief Summary

The primary objectives of this study are to evaluate the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in pediatric and adolescent participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL) or relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). As of October 2022, no further patients with acute B-cell Acute Lymphoblastic Leukemia (ALL) will be asked to join the study. The study remains open for recruitment for patients that have B-cell Non Hodgkin Lymphoma (NHL).

Conditions

Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia; Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Phase 1: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLT)

  Dose-limiting toxicity is defined as protocol-defined brexucabtagene autoleucel (KTE-X19)-related events with onset within the first 28 days following brexucabtagene autoleucel (KTE-X19) infusion.

  Up to 28 days

• Phase 2: Overall Complete Remission Rate in the ALL Cohort

  Overall complete remission rate will be determined per independent review.

  Up to 24 months

• Phase 2: Objective Response Rate in the NHL Cohorts

  Objective Response Rate will be determined per investigator review.

  Up to 24 months

Secondary Outcomes (11)

• Minimum Residual Disease Negative Remission Rate in the ALL Cohort

  Up to 3 months

• Allogeneic Stem Cell Transplant Rate in the ALL Cohort

  Up to 24 months

• Changes Over Time in Patient Reported Outcomes (PRO) Scores in the ALL and NHL Cohorts

  Up to 10 years

• Overall Complete Remission Rate in the ALL Cohort

  Up to 10 years

• Relapse-Free Survival for the ALL Cohort

  Up to 24 months

Study Arms (1)

Single Arm

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR+ T cells/kg or 1 x 10\^6 anti-CD19 CAR+ T cells/kg.

Biological: Brexucabtagene Autoleucel (KTE-X19); Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Brexucabtagene Autoleucel (KTE-X19) BIOLOGICAL

Single Arm

Fludarabine DRUG

Administered intravenously

Single Arm

Cyclophosphamide DRUG

Administered intravenously

Single Arm

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Relapsed or refractory B-precursor ALL defined as one of the following:
• Primary refractory disease
• Any relapse within 18 months after first diagnosis
• Relapsed or refractory disease after 2 or more lines of systemic therapy
• Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from stem cell transplant at the time of enrollment
• Disease burden defined as at least 1 of the following:
• Morphological disease in the bone marrow (\> 5% blasts)
• Minimal/Measurable Residual Disease (MRD) positive (threshold 10\^-4 by flow or Polymerase chain reaction (PCR))
• Individuals with Ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs
• Age ≤ 21 years and weight ≥ 6 kg at the time of assent or consent per Institutional Review Board (IRB) guidelines
• Lansky (age \< 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 80 at screening
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
• Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) ≥ 60 mL/min
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN, except in individuals with Gilbert's syndrome

You may not qualify if:

• Diagnosis of Burkitt's leukemia/lymphoma according to the World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
• History of severe hypersensitivity reaction to aminoglycosides or any of the agents used in this study
• Central nervous system (CNS) involvement and abnormalities:
• Any CNS tumor mass by imaging and/or parameningeal mass (cranial and/or spinal)
• Presence of central nervous system (CNS)-3 disease, defined as white blood cell (WBC) ≥ 5/µL in Cerebrospinal Fluid (CSF) with presence of lymphoblasts with or without neurologic symptoms
• CNS-2 disease, defined as WBC \< 5/µL in CSF with presence of lymphoblasts and with neurologic symptoms (see note below for further clarification).
• Note: Neurologic symptoms may include but are not limited to cranial nerve palsy (if not explained by extracranial tumor) and clinical cord compression.
• (Individuals with CNS-1 (no detectable lymphoblasts in the CSF) and those with CNS-2 without clinically evident neurological changes are eligible to participate in the study)
• History or presence of CNS disorder, such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema with confirmed structural defects not related to lymphoma by appropriate imaging. History of stroke or transient ischemic attack within 12 months before enrollment. Individuals with seizure disorders requiring active anticonvulsive medication.
• History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• Primary immunodeficiency
• History of human immunodeficiency virus (HIV) infection or acute / chronic active hepatitis B or C infection. Individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America guidelines or applicable country guidelines.

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (30)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

University of Miami Hospital & Clinics

Miami, Florida, 33136, United States

Location

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Columbia University Irving Medical Center/Morgan Stanley Children's Hospital-NYP

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Monroe-Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Health System, Pediatric Hematology/Oncology Clinic

Charlottesville, Virginia, 22908, United States

Location

University Hospital Gent

Ghent, 9000, Belgium

Location

The Hospital for Sick Children

Toronto, M5G 1X8, Canada

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

Unité d'Oncologie et Hématologie Pédiatriques

Bordeaux, 33 000, France

Location

Institut d'Hematologie et Oncologie Pediatrique

Lyon, 69373, France

Location

Hopital d'Enfants la Timone

Marseille, 13385, France

Location

Hopital Robert Debre - Sevice d'Hemato-immunologic

Paris, 75935, France

Location

University Medical Center Hamburg-Eppendorf (UKE)

Hamburg, 20246, Germany

Location

Bambino Gesù Children's Hospital

Rome, 00165, Italy

Location

Prinses Maxima Centrum

Utrecht, 3508, Netherlands

Location

Jurasz University Hospital 1; Collegium Medicum

Bydgoszcz, 85-094, Poland

Location

Wroclaw Medical University

Wroclaw, 50-556, Poland

Location

Hospital Sant Joan de Déu

Barcelona, 08950, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Karolinska University Hospital

Stockholm, SE-141 86, Sweden

Location

Related Publications (1)

• Wayne AS, Huynh V, Hijiya N, Rouce RH, Brown PA, Krueger J, Kitko CL, Ziga ED, Hermiston ML, Richards MK, Baruchel A, Schuberth PC, Rossi J, Zhou L, Goyal L, Jain R, Vezan R, Masouleh BK, Lee DW. Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia. Haematologica. 2023 Mar 1;108(3):747-760. doi: 10.3324/haematol.2022.280678.

  PMID: 36263840 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

brexucabtagene autoleucel; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

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: December 5, 2015
• First Posted: December 9, 2015
• Study Start: February 1, 2016
• Primary Completion: March 25, 2026
• Study Completion: March 25, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion and at least 6 months after the FDA and EMA approval
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

BE (1); CA (1); US (15); CZ (1); FR (4); NL (1); DE (1); ES (2); SE (1); PL (2); IT (1)