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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

Phase 1
Active, not recruiting
Conditions
Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Interventions
Biological: Brexucabtagene Autoleucel (KTE-X19)
Drug: Fludarabine
Drug: Cyclophosphamide
Registration Number
NCT02625480
Lead Sponsor
Kite, A Gilead Company
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).

Detailed Description

All participants who received KTE-X19, and have completed at least 24 months of protocol assessments, will be transitioned to a separate long-term follow-up (LTFU) study. The purpose of the LTFU study (KT-US-982-5968.) is to complete the remainder of the 15-year follow-up assessments.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
95
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single ArmBrexucabtagene Autoleucel (KTE-X19)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
Single ArmFludarabineA 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
Single ArmCyclophosphamideA 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
Primary Outcome Measures
NameTimeMethod
Phase 2: Overall Complete Remission Rate in the ALL CohortUp to 24 months

Overall complete remission rate will be determined per independent review.

Phase 1: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLT)Up to 28 days

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.

Phase 2: Objective Response Rate in the NHL CohortsUp to 24 months

Objective Response Rate will be determined per investigator review.

Secondary Outcome Measures
NameTimeMethod
CR Rate Within 3 Months Per Independent Review in ALL CohortsUp to 15 years
Minimum Residual Disease Negative Remission Rate in the ALL CohortUp to 3 months

Minimal residual disease (MRD) response rate is defined as MRD \< 10\^-4 per the standard assessment.

Changes Over Time in Patient Reported Outcomes (PRO) Scores in the ALL and NHL CohortsUp to 15 years

The PRO scores will be measured by the Pediatric Quality of Life Inventory (PedsQL) for children and adolescents and European Quality-of-Life-5 Dimension (EQ-5D) for all participants.

The PedsQL comprises of 23 items in the dimensions of physical, emotional, social, and school functioning. Transformed total, physical health summary, and psychosocial health summary scores range from 0-100 with higher scores indicating better health-related quality of life.

The EQ-5D is a generic questionnaire for assessing the participant's overall health status. The EQ-5D consists of a 5 dimension descriptive system including mobility, self-care, usual activities, pain/comfort, and anxiety/depression and a visual analogue scale (EQ-VAS) which allows the respondent to record health. The VAS allows a participant to indicate self-reported health on a vertical scale, ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The PedsQL scores and EQ-5D scores will be reported.

Overall Survival in the ALL and NHL CohortsUp to 15 years

Overall survival is defined as the time from brexucabtagene autoleucel (KTE-X19) infusion to the date of death from any cause.

Allogeneic Stem Cell Transplant Rate in the ALL CohortUp to 24 months

The incidence of allogeneic stem cell transplant will be analyzed.

Overall Complete Remission Rate in the ALL CohortUp to 15 years
Percentage of Participants with Anti-Brexucabtagene Autoleucel (KTE-X19) Antibodies in Blood in the ALL and NHL CohortsUp to 15 years
Relapse-Free Survival for the ALL CohortUp to 24 months

Relapse-Free Survival is defined as the time from the brexucabtagene autoleucel (KTE-X19) infusion date to the date of disease relapse or death from any cause.

Progression Free Survival in the NHL CohortUp to 15 years
Duration of Remission in the ALL and NHL CohortsUp to 24 months

Duration of remission is defined as the time between the participant's first complete response per independent review to relapse or any death in the absence of documented relapse.

Percentage of Participants Experiencing Adverse Events and Common Terminology Criteria for Adverse Events (CTCAE) Grade Changes in Safety Laboratory Values in ALL and NHL CohortsUp to 15 years

Trial Locations

Locations (30)

Ann & Robert H. Lurie Children's Hospital

🇺🇸

Chicago, Illinois, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

University of Miami Hospital & Clinics

🇺🇸

Miami, Florida, United States

UCSF Benioff Children's Hospital

🇺🇸

San Francisco, California, United States

Monroe-Carell Jr. Children's Hospital at Vanderbilt

🇺🇸

Nashville, Tennessee, United States

The Hospital for Sick Children

🇨🇦

Toronto, Canada

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Jurasz University Hospital 1; Collegium Medicum

🇵🇱

Bydgoszcz, Poland

Wroclaw Medical University

🇵🇱

Wroclaw, Poland

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

🇺🇸

New York, New York, United States

University Medical Center Hamburg-Eppendorf (UKE)

🇩🇪

Hamburg, Germany

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

Hopital Robert Debre - Sevice d'Hemato-immunologic

🇫🇷

Paris Cedex 19, France

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Children's Hospitals and Clinics of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

The Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

University of Virginia Health System, Pediatric Hematology/Oncology Clinic

🇺🇸

Charlottesville, Virginia, United States

University Hospital Gent

🇧🇪

Gent, Belgium

The University of Texas M.D. Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University Hospital Brno

🇨🇿

Brno, Czechia

Unité d'Oncologie et Hématologie Pédiatriques

🇫🇷

Bordeaux, France

Institut d'Hematologie et Oncologie Pediatrique

🇫🇷

Lyon, France

Hopital d'Enfants la Timone

🇫🇷

Marseille Cedex 5, France

Hospital Sant Joan de Déu

🇪🇸

Barcelona, Spain

Bambino Gesù Children's Hospital

🇮🇹

Rome, Italy

Prinses Maxima Centrum

🇳🇱

Utrecht, Netherlands

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Kapi'olani Medical Center for Women and Children

🇺🇸

Honolulu, Hawaii, United States

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