SHS_492337 PAGJ CKIT 16051

A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)

This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL).

Inclusion Criteria:

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
Morphological disease in the bone marrow (≥ 5% blasts)
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
Age 18 or older
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
Adequate renal, hepatic, pulmonary and cardiac function defined as:
Creatinine clearance ≥ 60 cc/min
Serum ALT/AST ≤ 2.5 x ULN
Total bilirubin ≤ 1.5 mg/dl
Cardiac ejection fraction ≥ 50% and no clinically significant ECG findings
Baseline oxygen saturation > 92% on room air

Exclusion Criteria

Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
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
Presence of CNS-3 disease or CNS-2 disease with neurological changes
History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
Primary immunodeficiency
Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
Prior medication:
Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug conjugate (ADC), with the exception of subjects who received KTE-C19 in this study and are eligible for re-treatment
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
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
Live vaccine ≤ 6 weeks prior to start of conditioning regimen
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
Subjects of both genders of child-bearing potential who are not willing to practice birth control from the time of consent through 6 months after the completion of KTE-C19
Phase I/II
John Pagel, M.D.
Kite Pharma, Inc
Neil Bailey
  • Swedish Medical Center