A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
- Conditions
- Acute Lymphoblastic LeukemiaCancer of white blood cells.10024324
- Registration Number
- NL-OMON54807
- Lead Sponsor
- Kite Pharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
101. Relapsed or refractory B-precursor ALL defined as one of the following:
o Primary refractory disease
o First relapse if first remission <= 12 months
o Relapsed or refractory disease after two or more lines of systemic therapy
o 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 >= 100/µL
109. Adequate renal, hepatic, pulmonary and cardiac function defined as:
o Creatinine clearance (as estimated by Cockcroft Gault) >= 60 cc/min
o Serum ALT/AST <= 2.5 x ULN (upper limit normal)
o Total bilirubin <= 1.5 mg/dl, except in subjects with Gilbert*s syndrome.
o Left ventricular ejection fraction (LVEF) >= 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
o No clinically significant pleural effusion
o 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 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.
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. 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, 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:
o Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL and
blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to
enrollment
o Prior CD19 directed therapy other than blinatumomab
o History of CTCAE grade 4 neurologic event or grade 4 CRS (Lee 2014) with
prior CD19-directed therapy
o Treatment with 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
o Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
o 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, anti-interleukin 6 or anti-interleukin 6
receptor)
o 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,
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>• Phase 1: Incidence of adverse events (AEs) defined as dose-limiting<br /><br>toxicities (DLTs) in the DLT evaluable set<br /><br>• Phase 2: Overall complete remission rate (CR + CRi) per independent<br /><br>review (Appendix A) as defined by;<br /><br>o Less than or equal to 5% blasts in the bone marrow, and<br /><br>o No other evidence of morphologic disease*, and either<br /><br>o Platelets >= 100,000/µL and ANC >=1,000/µL (CR) or<br /><br>o Platelets < 100,000/µL and ANC >= 1000/µL or Platelets >= 100,000/µL and ANC <<br /><br>1000/µL but not CR (CRi).<br /><br><br /><br>*All subjects must demonstrate a negative CSF assessment to be considered to<br /><br>achieve CR or CRi. Subjects with extramedullary disease detected through<br /><br>imaging at baseline also must meet the criteria for CR per Cheson 2007<br /><br>(Appendix A of KTE-C19-103 study protocol) in order to be considered to have CR<br /><br>or CRi. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>• Overall complete remission rate (CR + CRi) per investigator assessment<br /><br>(Appendix A)<br /><br>• Duration of Remission (DOR)<br /><br>• Minimal Residual Disease (MRD) negative rate<br /><br>• Allogeneic stem cell transplant (Allogeneic SCT) rate<br /><br>• Overall survival (OS)<br /><br>• Relapse-free Survival (RFS)<br /><br>• Incidence of AEs and common terminology criteria for adverse events (CTCAE)<br /><br>grade changes in safety laboratory values<br /><br>• Incidence of anti-KTE-X19 antibodies<br /><br>• Changes over time in the EQ-5D score and VAS score (phase 2 only).</p><br>