Purpose

The primary objectives of this study are to evaluate the safety and efficacy of 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).

Conditions

Eligibility

Eligible Ages
Under 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

for the ALL Cohort

- Relapsed or refractory B-precursor ALL defined as one of the following:

- Primary refractory disease

- 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

- Morphological disease in the bone marrow (> 5% blasts)

- 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 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 ≥ 60 cc/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 ECHO and no clinically significant arrhythmias

- No clinically significant pleural effusion

- Baseline oxygen saturation > 92% on room air

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

- Presence of central nervous system (CNS)-3 disease and CNS-2 disease with neurological changes

- 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

- Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)

- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.

- Prior medication:

- Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug conjugate (ADC), with the exception of individuals who received 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 ≤ 4 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 practice birth control from the time of consent through 6 months after the completion of KTE-X19

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 subject 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

- 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 cc/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 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

- History of HIV infection or acute /chronic 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

- CNS abnormalities

- Presence of CNS-3 disease, defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 with or without neurological changes or presence of CNS-2 disease with neurological symptoms (see note below for further clarification), defined as detectable cerebrospinal blast cells in a sample of CSF with < 5 WBCs per mm^3 with neurological changes

- Note: Individuals with CNS-1 (no detectable blast cells in the CSF) and those with CNS-2 without clinically evident ne urological 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

- 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 who are not willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Single Arm
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of 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: KTE-X19
  • Drug: Fludarabine
    Administered intravenously
  • Drug: Cyclophosphamide
    Administered intravenously

Recruiting Locations

Vanderbilt University
Nashville, Tennessee 37232
Contact:
Eugenia (Gina) Owens
eugenia.owens@Vanderbilt.Edu

More Details

NCT ID
NCT02625480
Status
Recruiting
Sponsor
Kite, A Gilead Company

Study Contact

Medical Information
1-844-454-5483(1-844-454-KITE)
medinfo@kitepharma.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.