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)
- Conditions
- Acute Lymphoblastic LeukemiaNon-Hodgkin Lyphoma10024324
- Registration Number
- NL-OMON54583
- Lead Sponsor
- Kite Pharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
ALL Cohort
101. 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 subject
is at least 100 days from stem cell transplant at the time of enrollment and
off of immunosuppressive medications for at least 4 weeks prior to enrollment
102. Disease burden defined as at least 1 of the following:
-Morphological disease in the bone marrow (>5% blasts)
-MRD positive (threshold 10-4 by flow or PCR)
103. Subjects 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
104. Age = 21 years and weight >= 6 kg.
Note: Subjects with a weight of >= 6 kg to < 10kg will only be included
once a pediatric formulation becomes available.
111. In subjects previously treated with blinatumomab, CD19 tumor expression on
blasts obtained from bone marrow or peripheral blood must be documented after
completion of the most recent prior line of therapy and blasts must be >= 90%
CD19 positive.
NHL Cohort
301. Histologically confirmed aggressive B cell NHL:
- DLBCL not otherwise specified
- Primary mediastinal large B-cell lymphoma (including Mediastinal gray zone
lymphoma)
- Burkitt lymphoma, Burkitt-like lymphoma and Unclassified B-cell lymphoma
intermediate between DLBCL and Burkitt lymphoma
302. Relapsed or refractory disease defined as 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 SCT provided
subject is at least 100 days from SCT at the time of enrollment and off of
immunosuppressive
medications for at least 4 weeks prior to enrollment
303. Subjects 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
304. At least 1 measurable lesion according to the revised International
Pediatric Non-Hodgkin Lymphoma Staging System {Rosolen 2015}. Lesions that have
been previously irradiated will be considered measurable only if progression
has been documented following completion of radiation therapy.
305. Magnetic resonance imaging (MRI) of the brain showing no evidence of CNS
lymphoma
308. Age <18 years old and weight > or = 6kg
Note: Subjects with a weight of >= 6 kg to < 10kg will only be included
once a pediatric formulation becomes available.
Both Cohort:
105. and 309. Lansky (age < 16 years at the time of assent/consent) or
Karnofsky (age > or = 16 years at the time of assent/consent) performance
status > or = 80 at screening
106. and 310. ANC > or = 500/uL unless, in the opinion of the PI,
cytopenia is due to underlying leukemia and is potentially reversible with
leukemia therapy
107. and 311. Platelet count > or = 50,000/uL unless, in the opinion of the PI,
cytopenia is due to underlying leukemia and is potentially reversible with
leukemia therapy
108.
ALL Cohort
201. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification
or chronic myelogenous leukemia lymphoid blast crisis
202. History of malignancy other than nonmelanoma skin cancer or carcinoma in
situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
204. CNS abnormalities
a. 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,
and presence of CNS-2 disease with neurological symptoms defined as detectable
cerebrospinal blast cells in a sample of CSF with < 5 WBCs per mm3 with
neurological changes
Note: Subjects with CNS-1 (no detectable leukemia in the CSF) and those with
CNS-2 without clinically evident neurological changes are eligible to
participate in the study.
b. History or presence of any CNS disorder such as a seizure disorder,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any
autoimmune disease with CNS involvement, posterior reversible encephalopathy
syndrome (PRES), or cerebral edema
205. History of concomitant genetic syndrome associated with bone marrow
failure such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome
206. History of myocardial infarction, cardiac angioplasty or stenting,
unstable angina, or other clinically significant cardiac disease within 12
months of enrollment
209. Known infection with human immunodeficiency virus (HIV), hepatitis B
virus, or hepatitis C virus. A history of hepatitis B or hepatitis C is
permitted if the viral load is undetectable per quantitative PCR and/or nucleic
acid testing.
NHL Cohort
401. History of malignancy other than nonmelanoma skin cancer, carcinoma in
situ (eg, cervix, breast), or FL unless disease free for at least 3 years
402. Autologous SCT within 100 days of planned KTE-X19 infusion
403. Prior CD19 targeted therapy other than blinatumomab (subjects who received
KTE-X19 in this study and are eligible for re-treatment)
404. Prior CAR therapy or other genetically modified T-cell therapy
407. History of HIV infection or acute /chronic hepatitis B or C infection.
Subjects 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
409. 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.
Both Cohort:
204. and 410. CNS involvement and abnormalities:
a. Any CNS tumor mass by imaging and/or parameningeal mass (cranial and/or
spinal).
b. Presence of CNS-3 disease, defined as WBC >=5/µL in CSF with presence of
lymphoblasts with or without neurologic symptoms.
c. 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.
[Subjects with CNS-1 (no detectable lymphoblasts in the CSF) and those with CNS
2 without clinically evident neurological changes are eligible to participate
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1:<br /><br>Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs).<br /><br><br /><br>Phase 2:<br /><br><br /><br>ALL Cohort:<br /><br>Overall complete remission rate (CR + CRi) per independent review. All subjects<br /><br>who do not meet the criteria for CR or CRi by the analysis data cutoff date<br /><br>will be considered non-responders for the overall complete remission rate<br /><br>evaluation.<br /><br><br /><br>NHL Cohort:<br /><br>ORR per investigator assessment</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>- Overall complete remission rate (CR + CRi) per investigator assessment<br /><br>- Duration of Remission (DOR) in the ALL and NHL cohort<br /><br>- Minimal Residual Disease (MRD) negative rate in ALL cohort<br /><br>- Allogeneic SCT rate<br /><br>- Overall survival (OS) in the ALL and NHL cohort<br /><br>- Relapsed-free Survival (RFS) in ALL cohort<br /><br>- Incidence of AEs and Common Terminology Criteria for Adverse Events (CTCAE)<br /><br>grade changes in safety laboratory values in the ALL and NHL cohort<br /><br>- Incidence of anti-KTE-X19 antibodies in the ALL and NHL cohort<br /><br>- Progression free survival in the NHL cohort</p><br>