A 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 Non-Hodgkin Lymphoma
- Conditions
- Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) Relapsed/Refractory B-cell non-Hodgkin lymphoma (r/r NHL)MedDRA version: 21.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10006595Term: Burkitt's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10036710Term: Primary mediastinal large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005010-30-PL
- Lead Sponsor
- Kite Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 116
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. and 312. Absolute lymphocyte count > or = 100/µL
109. and 313. Adequate renal, hepatic, pulmonary and cardiac function
110. and 314. Females of childbearing potential must have a negative serum or ur
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
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
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 are eligible for re-treatment)
404. Prior CAR therapy or other genetically modified T-cell therapy
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 in the study].
d. History or presence of any 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. Patients with seizure disorders requiring active anti-convulsive medication.
208. and 416. Any medical condition likely to interfere with assessment of the safety or efficacy of study treatment
209. and 414. Primary immunodeficiency
210. and 407. History of HIV infection or acute /chronic active 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method