A Study Evaluating the Safety and Effectiveness of KTE-C19 in Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia.
- Conditions
- Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL)MedDRA version: 20.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000012958Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005009-35-FR
- Lead Sponsor
- Kite Pharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
101. Relapsed or refractory B-precursor ALL defined as one of the following:
- Primary refractory disease
- First relapse if first remission = 12 months
- Relapsed or refractory disease after first or later salvage 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. 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. Age 18 or older
105. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
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 = 200/µL
109. Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) = 60 cc/min
- Serum ALT/AST = 2.5 x ULN
- Total bilirubin = 1.5 mg/dl, except in subjects with Gilbert’s syndrome.
- Cardiac ejection fraction = 50%, no evidence of pericardial effusion as determined by an ECHO, no NYHA class III or class IV functional classification, and no clinically significant arrhythmias
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
110. Females of childbearing potential must have a negative serum or urine pregnancy test
111. In subjects previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood must be documented after completion of the most recent prior line of therapy. If CD19 expression is quantified, then there must be = 90% CD19 positive blasts.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
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 non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
203. Isolated extramedullary disease
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
205. History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure 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 chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
- Prior CD19 directed therapy other than blinatumomab
- 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 GVHD within 4 weeks prior to enrollment (e.g. calcineurin inhibitors, methotrexate, mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as rituximab, anti-tumor necrosis factor, anti-interleukin 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 (> 5 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to enrollment
212. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
213. Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or
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