Non Hodgkin Lymphoma Clinical Trial

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

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).

View Eligibility Criteria

Eligibility Criteria

Key Inclusion Criteria for the ALL Cohort

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

Note: Individuals with a weight of ≥ 6 kg to < 10kg will only be included once a pediatric formulation becomes available.
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
Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria for the ALL Cohort

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 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
Relapsed or refractory disease after 2 or more lines of systemic therapy
Relapsed or refractory disease after autologous /allogeneic transplant provided individual is at least 100 days from 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

Note: Individuals with a weight of ≥ 6 kg to < 10kg will only be included once a pediatric formulation becomes available.
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
Prior CD19 targeted therapy other than blinatumomab
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 by imaging and/or parameningeal mass (cranial and/or spinal)
Presence of CNS-3 disease, defined as WBC ≥ 5/µL in CSF with presence of lymphoblasts with or without neurologic symptoms.
Presence of 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 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 conditioning 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 6 months after the completion of conditioning 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.

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

116

Study ID:

NCT02625480

Recruitment Status:

Active, not recruiting

Sponsor:

Kite, A Gilead Company

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There are 30 Locations for this study

See Locations Near You

Children's Hospital Los Angeles
Los Angeles California, 90027, United States
Children's Hospital of Orange County
Orange California, 92868, United States
UCSF Benioff Children's Hospital
San Francisco California, 94158, United States
University of Miami Hospital & Clinics
Miami Florida, 33136, United States
Kapi'olani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States
Ann & Robert H. Lurie Children's Hospital
Chicago Illinois, 60611, United States
Johns Hopkins University
Baltimore Maryland, 21287, United States
Children's Hospitals and Clinics of Minnesota
Minneapolis Minnesota, 55404, United States
Columbia University Irving Medical Center/Morgan Stanley Children's Hospital-NYP
New York New York, 10032, United States
University of Rochester Medical Center
Rochester New York, 14642, United States
The Children's Hospital of Philadelphia
Philadelphia Pennsylvania, 19104, United States
Monroe-Carell Jr. Children's Hospital at Vanderbilt
Nashville Tennessee, 37232, United States
Texas Children's Hospital
Houston Texas, 77030, United States
The University of Texas M.D. Anderson Cancer Center
Houston Texas, 77030, United States
University of Virginia Health System, Pediatric Hematology/Oncology Clinic
Charlottesville Virginia, 22908, United States
University Hospital Gent
Gent , 9000, Belgium
The Hospital for Sick Children
Toronto , M5G 1, Canada
University Hospital Brno
Brno , 625 0, Czechia
Unité d'Oncologie et Hématologie Pédiatriques
Bordeaux , 33 00, France
Institut d'Hematologie et Oncologie Pediatrique
Lyon , 69373, France
Hopital d'Enfants la Timone
Marseille Cedex 5 , 13385, France
Hopital Robert Debre - Sevice d'Hemato-immunologic
Paris Cedex 19 , 75935, France
University Medical Center Hamburg-Eppendorf (UKE)
Hamburg , 20246, Germany
Klinikum Innenstadt der LMU
Munich , 80337, Germany
Bambino Gesù Children's Hospital
Rome , 00165, Italy
Prinses Maxima Centrum
Utrecht , 3508, Netherlands
Jurasz University Hospital 1; Collegium Medicum
Bydgoszcz , 85-09, Poland
Wroclaw Medical University
Wroclaw , 50-55, Poland
Hospital Sant Joan de Déu
Barcelona , 08950, Spain
Hospital Universitario La Paz
Madrid , 28046, Spain
Karolinska University Hospital
Stockholm , SE-14, Sweden

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

116

Study ID:

NCT02625480

Recruitment Status:

Active, not recruiting

Sponsor:


Kite, A Gilead Company

How clear is this clinincal trial information?

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