Overview
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
Status:
Recruiting
Recruiting
Trial end date:
2038-08-01
2038-08-01
Target enrollment:
0
0
Participant gender:
All
All
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).Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Kite, A Gilead CompanyTreatments:
Cyclophosphamide
Fludarabine
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.