Clinical Trials

Inclusion Criteria:

1. Relapsed or refractory B-precursor ALL defined as one of the following:
   • Primary refractory disease
   • 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
2. Morphological disease in the bone marrow (≥ 5% blasts)
3. 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
4. Ages 2 to 21 at the time of Assent or Consent per IRB guidelines
5. 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
6. 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 x ULN
   • Cardiac ejection fraction ≥ 50% and no clinically significant ECG findings
   • Baseline oxygen saturation > 92% on room air

Exclusion Criteria

1. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
2. 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
3. Presence of CNS-3 disease and CNS-2 disease with neurological changes
4. History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
6. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
7. Primary immunodeficiency
8. Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
9. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
10. Prior medication:
    • Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug conjugate (ADC), with the exception of subjects who received KTE-X19 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
11. 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
12. Live vaccine ≤ 6 weeks prior to start of conditioning regimen
13. 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
14. 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