A Study Evaluating the Safety and Efficacy of KTE-C19 in pediatric and adolescent Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
- Conditions
- Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL)MedDRA version: 20.1Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005010-30-NL
- 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
- 100
101. 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 subject is at least 100 days from stem cell transplant at the time of enrollment and off immunosuppressive medications for at least 4 weeks prior to enrollment
102. Morphological disease in the bone marrow (> 5% blasts)
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. Ages 2-21 at the time of Assent or Consent per IRB guidelines
105. 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 (Appendix C)
106. ANC = 500/uL unless in the opinion of the PI cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy
107. Platelet count = 50,000/uL unless in the opinion of the PI cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy
108. Absolute lymphocyte count = 100/µL
109. Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) = 60 cc/min
- Serum ALT and AST = 5 x ULN
- Total bilirubin = 1.5 x ULN, except in subjects with Gilbert’s syndrome.
- LVSF = 30% or LVEF = 50%, no evidence of pericardial effusion as determined by an ECHO and no clinical significant arrhythmias
- No clinically significant pleural effusion
- Baseline oxygen saturation = 92% on room air
110. Females of childbearing potential (defined as having first menses) must have a negative serum or urine pregnancy test
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. If CD19 expression is quantified, then blasts must be = 90% CD19 positive.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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
203. History of severe hypersensitivity reaction to aminoglycosides or any of the agents used in this study
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 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
207. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
208. Primary immunodeficiency
209. Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
210. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor
211. Prior medication:
- Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL, and blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to enrollment
- Prior CD19 directed therapy other than blinatumomab
- History of Grade 4 neurologic event (Common Terminology Criteria for Adverse Events [CTCAE]) or Grade 4 CRS (Lee et al, 2014) with prior CD19-directed therapy
- Alemtuzumab within 6 months prior to enrollment, clofarabine or cladribine within 3 months prior to enrollment, or PEG-asparaginase within 3 weeks prior to enrollment
- Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
- Any drug used for GVHD within 4 weeks prior to enrollment (eg, calcineurin inhibitors, methotrexate, mycophenolyate, rapamycin, thalidomide) or immunosuppressive antibody used within 4 weeks prior to enrollment (eg, anti-CD20, anti-tumor necrosis factor [TNF], anti-interleukin [IL] 6 or anti-interleukin 6 receptor)
- At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists etc)
- Corticosteroid therapy at a pharmacologic dose (= 0.7 mg/kg/day of hydrocortisone or equivalent doses of corticosteroids) and other immunosuppressive dru
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