A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-4)
The primary objectives of this study are to evaluate the safety and efficacy of KTE-C19 in pediatric and adolescent participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).
2 Years to 21 Years
Accepting Healthy Volunteers?
- 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 individual is at least 100 days from stem cell transplant at the time of enrollment
- Morphological disease in the bone marrow (> 5% blasts)
- Individuals 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
- Ages 2 to 21 at the time of Assent or Consent per institutional review board (IRB) guidelines
- 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
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine clearance ≥ 60 cc/min
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN, except in individuals with Gilbert's syndrome
- Left ventricular shortening fraction (LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram, and no clinical significant arrhythmias
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria
- Diagnosis of Burkitt's leukemia/lymphoma according to the World Health Organization (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
- History of severe hypersensitivity reaction to aminoglycosides or any of the agents used in this study
- Presence of central nervous system (CNS)-3 disease and 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 individuals 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 graft-versus-host disease (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 are not considered to be of childbearing potential
- Individuals 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.