Study Details

OVERVIEW

A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia or Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (ZUMA-4) (ZUMA-4)

PROTOCOL 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).

Participation Requirements

Age

0 - 21 Years

Sex

All

Healthy Volunteers

Medical Condition

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

Gender

N/A

Date

February 2016 - December 2025

Study Type

Interventional

Study Phase

Phase 1, Phase 2

Product

Brexucabtagene Autoleucel (KTE-X19), Fludarabine, Cyclophosphamide

Eligibility Information

Inclusion Criteria

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
Left ventricular shortening fraction (LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%, as determined by an echocardiogram or multi-gated acquisition scan (MUGA), no evidence of pericardial effusion (except trace or physiological) as determined by an echocardiogram (ECHO) and no clinically significant arrhythmias
No clinically significant pleural effusion, pericardial effusion or ascites
Baseline oxygen saturation > 92% on room air

Exclusion Criteria

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.
Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
Prior medication:
Prior CD19 directed therapy (other than blinatumomab), including CAR+ T cell, bispecific T cell engager (BiTE), and antibody drug conjugate (ADC), with the exception of individuals who received brexucabtagene autoleucel (KTE-X19) in this study and are eligible for re-treatment
Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
Any drug used for graft-versus-host disease (GVHD) within 4 weeks prior to enrollment
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
Live vaccine ≤ 6 weeks prior to enrollment
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization are not considered to be of childbearing potential
Individuals of both genders of child-bearing potential who are not willing to use a birth control method considered to be highly effective per protocol from the time of consent through 6 months after conditioning chemotherapy or brexucabtagene autoleucel (KTE-X19) infusion, whichever is longer.
Key Inclusion Criteria for the NHL Cohort
Histologically confirmed aggressive B cell NHL
Relapsed or refractory histologically confirmed aggressive B-cell NHL per 1 or more of the following:
Primary refractory disease
Any relapse within 18 months after first diagnosis
Relapsed or refractory disease after 1 or more lines of systemic therapy
Relapsed or refractory disease after autologous /allogeneic stem cell transplant provided individual is at least 6 weeks from autologous stem cell transplant and at least 3 months from allogeneic stem cell transplant at the time of enrollment
Individuals must have received adequate prior therapy including at a minimum all of the following:
Anti-CD20 monoclonal antibody, unless the investigator determines that the tumor is CD20 negative
An anthracycline-containing chemotherapy regimen
Age <18 years old and weight ≥ 6kg
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 the following:
Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) ≥ 60 mL/min
Serum ALT/AST ≤ 5 ULN
Total bilirubin ≤1.5 x ULN except in individuals with Gilbert's syndrome
Left ventricular shortening fraction(LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%, as determined by ECHO or MUGA, no evidence of pericardial effusion (except trace or physiological) as determined by an ECHO, and no clinically significant arrhythmias
Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria for the NHL Cohort
History of malignancy other than nonmelanoma skin cancer, carcinoma in situ (eg, cervix, breast), or follicular lymphoma (FL) unless disease free for at least 3 years
Autologous stem cell transplant within <6 weeks of planned KTE-X19 infusion; allogeneic stem cell transplant within <3 months of planned KTE-X19 infusion
Prior CD19 targeted therapy other than blinatumomab and loncastuximab tesirine-lpyl
History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
History of 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
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by International Bone Marrow Transplant Registry (IBMTR) index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment.
CNS involvement and abnormalities:
Any CNS tumor mass and/or parameningeal mass (cranial and/or spinal) by imaging with current or prior history of neurological symptoms within 3 months prior to screening.
Note: CNS involvement without neurologic symptoms will be allowed.
History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months before enrollment. Individuals with seizure disorders requiring active anti-convulsive medication.
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
Primary immunodeficiency
History of severe immediate hypersensitivity reaction to any of the agents used in this study
Live vaccine ≤ 6 weeks prior to planned start of lymphodepleting chemotherapy regimen
Individuals of both genders of child-bearing potential who are not willing to use a birth control considered to be highly effective per protocol from the time of consent through 12 months after the completion of lymphodepleting chemotherapy or brexucabtagene autoleucel (KTE-X19) infusion, whichever is longer.
Prior medication:
Prior CD19 directed therapy (other than blinatumomab), including CAR+ T cell, BiTE, and ADC, with the exception of individuals who received brexucabtagene autoleucel (KTE-X19) in this study and are eligible for re-treatment
Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
DLI within 28 days prior to enrollment
Any drug used for GVHD within 4 weeks prior to enrollment
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations

Locations (37)

City of Hope

Duarte, California, United States, 91010

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Children's Hospital of Orange County

Orange, California, United States, 92868

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94158

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

University of Miami Hospital & Clinics

Miami, Florida, United States, 33136

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, United States, 96826

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, United States, 60611

University of Chicago

Chicago, Illinois, United States, 60637

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States, 55404

Mayo Clinic

Rochester, Minnesota, United States, 55902

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

New York, New York, United States, 10032

University of Rochester Medical Center

Rochester, New York, United States, 14642

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Monroe-Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States, 37232

Texas Children's Hospital

Houston, Texas, United States, 77030

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States, 77030

University of Virginia Health System, Pediatric Hematology/Oncology Clinic

Charlottesville, Virginia, United States, 22908

Medical College of Wisconsin (Administrative Offices)

Milwaukee, Wisconsin, United States, 53226

University Hospital Gent

Gent, Belgium, 9000

The Hospital for Sick Children

Toronto, Canada, M5G 1X8

University Hospital Brno

Brno, Czechia, 625 00

Unité d'Oncologie et Hématologie Pédiatriques

Bordeaux, France, 33 000

Institut d'Hematologie et Oncologie Pediatrique

Lyon, France, 69373

Hopital d'Enfants la Timone

Marseille Cedex 5, France, 13385

Hopital Robert Debre - Sevice d'Hemato-immunologic

Paris Cedex 19, France, 75935

University Medical Center Hamburg-Eppendorf (UKE)

Hamburg, Germany, 20246

Klinikum Innenstadt der LMU

Munich, Germany, 80337

Bambino Gesù Children's Hospital

Rome, Italy, 00165

Prinses Maxima Centrum

Utrecht, Netherlands, 3508

Jurasz University Hospital 1; Collegium Medicum

Bydgoszcz, Poland, 85-094

Wroclaw Medical University

Wroclaw, Poland, 50-556

Hospital Sant Joan de Déu

Barcelona, Spain, 08950

Hospital Universitario La Paz

Madrid, Spain, 28046

Karolinska University Hospital

Stockholm, Sweden, SE-141 86

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 (ZUMA-4)