A Phase 1/2 Multicenter Study of KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia.

Phase 1

Conditions: Relapsed/Refractory Chronic Lymphocytic Leukemia
MedDRA version: 21.1Level: LLTClassification code 10008977Term: Chronic lymphocytic leukemia recurrentSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10008978Term: Chronic lymphocytic leukemia refractorySystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-001923-38-GB

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: 16

Inclusion Criteria

101. Documentation of relapsed or refractory CLL; subjects must have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor
102. An indication for treatment per IWCLL 2018 criteria and radiographically measurable disease (at least 1 lesion > 1.5cm in diameter)
103. Adequate hematologic function
104. Adequate renal, hepatic, cardiac and pulmonary function
105. Age 18 or older
106. ECOG performance status of 0 or 1
107. Females of childbearing potential must have a negative serum or urine pregnancy test
108. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists)
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 78

Exclusion Criteria

201. A history of treatment including any of the following:
a. Prior CD19 directed therapy
b. Treatment with alemtuzumab within 6 months before enrollment
c. Prior allogeneic hematopoietic stem cell transplant or donor lymphocyte infusion within 6 months prior to enrollment
d. Live vaccine administration within 4 weeks before enrollment
e. Systemic immunosuppression or systemic treatment for any autoimmune disease not related to CLL in the 2 years before enrollment
202. Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index
203. History of autoimmune disease resulting in end-organ injury unless attributable to CLL (eg, ITP, AIHA)
204. Diagnosis of Richter's transformation or a history of malignancy. Exceptions include: non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast), superficial bladder cancer, asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care, or any other cancer that has been in remission for > 3 years prior to enrollment205. History of severe hypersensitivity reaction attributed to aminoglycosides or any of the agents required for treatment in this study
206. CNS disease
207. History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
208. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months before enrolment
209. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment
210. Primary immunodeficiency
211. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Disease Society of America (IDSA) guidelines or applicable country guidelines.212. Presence of active fungal, bacterial, viral infection or any infection requiring antimicrobial treatment for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite Medical Monitor
213. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are permitted
217. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase 1: Evaluate the safety of KTE-X19 <br>Phase 2: Evaluate the efficacy of KTE-X19 as measured by the objective response rate (ORR) per independent review ;Secondary Objective: Characterize the safety profile and assess additional efficacy endpoints ;Primary end point(s): Phase 1: Incidence of DLTs in subjects treated with KTE-X19 <br>Phase 2: Objective response rate (CR/CRi/PR) per independent review as defined by IWCLL 2018 criteria;Timepoint(s) of evaluation of this end point: Phase 1: onset within the first 28 days following KTE-X19 infusion<br>Phase 2: Disease assessment at D28, W8, M3, M6, then every 3 months till M24

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Complete response (CR/CRi) rate,<br>ORR per investigator review<br>Minimum Residual Disease (MRD) Negative Rate<br>CR/CRi with MRD- (CR/MRD-) rate<br>Duration of response (DOR), <br>Progression-free survival (PFS)<br>Overall survival (OS)<br>Incidence of AEs and clinically significant changes in laboratory values<br>Changes in EQ-5D and FACT-Leu<br>Levels of anti-CD19 CAR T-cells in blood;Timepoint(s) of evaluation of this end point: Disease Assessment at D28, W8, M3, M6, then every 3 months till M24, then every 6 months till M60, them annually through Year 15<br>Blood draw at leukapheresis, M3, and every 3 months up to M12 if applicable<br>Safety: onset on or after the KTE-X19 infusion, through the study

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