KTE-X19 with Conditioning Chemotherapy for the Treatment of Patients with MRD Positive B-Cell Acute Lymphoblastic Leukemia Following Induction Therapy

Inclusion Criteria

• Must be an adult 18 years of age or older
• Pathologically confirmed CD19 positive B-cell acute lymphoblastic leukemia, as defined by local institution, at diagnosis
• Treatment and full recovery from induction chemotherapy, with following exceptions: * Vincristine associated grade 1 peripheral neuropathy * Steroid/asparaginase associated diabetes and/or hypertension * Inotuzumab/chemotherapy associated cytopenias (though must still meet inclusion criteria below)
• Patients must be in a complete remission with MRD following an induction regimen
• Induction therapy options are described below: * Induction options for Philadelphia chromosome negative B-ALL include cycle 1A of cyclophosphamide, vincristine, doxorubicin and dexamethasone (HyperCVAD) +/- rituximab, cycle 1A of mini-Hyper-CVD + inotuzumab +/- rituximab, CALGB 10403 defined induction (+/- extended induction), and the Dana Farber Cancer Institute (DFCI) elderly protocol defined induction. It is understood that each regimen includes central nervous system (CNS) prophylaxis and may require dose modification. Patients requiring consolidation therapy to achieve MRD are not permitted * Induction options for Philadelphia chromosome positive B-ALL include cycle 1A of HyperCVAD + tyrosine kinase inhibitor (TKI) +/- rituximab, or cycle 1A of mini-Hyper-CVD + TKI +/- rituximab. Commonly used tyrosine kinase inhibitors include ponatinib (30-45mg PO daily), dasatinib (100-140mg PO daily), and imatinib (400-600mg PO daily). It is understood that each regimen includes CNS prophylaxis and may require dose modification. Patients requiring consolidation therapy to achieve MRD are not permitted
• MRD is defined herein as a bone marrow biopsy with fewer than 5% lymphoblasts, quantifiable by the ClonoSeq assay
• Complete remission implies the resolution of any extramedullary and/or CNS-2-3/parenchymal disease
• Be willing and able to provide written informed consent/assent for the trial
• Able to adhere to the study visit schedule and other protocol requirements
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Serum bilirubin and creatinine < 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be <3 x ULN
• Left ventricular ejection fraction (LVEF) > 50%
• Oxygen saturation > 92% (on room air)
• Absolute neutrophil count ≥ 1000 /ul (in the absence growth factor supplementation in the preceding 7 days)
• Hemoglobin ≥ 8 gm/dL (in the absence of transfusion in the preceding 7 days)
• Platelet count ≥ 50,000 /ul (in the absence of transfusion in the preceding 7 days)
• Absolute lymphocyte count ≥ 100 /ul
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening. A FCBP is considered when a sexually mature female: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months
• Subjects of both genders of child-bearing potential must be willing to practice birth control from the time of consent through 6 months after the completion of KTE-X19 infusion

Exclusion Criteria

• Diagnosis of L3 type Burkitt’s lymphoma, mixed lineage leukemia (MLL) rearranged leukemia, biphenotypic leukemia, mixed phenotype acute leukemia, blast phase of chronic myeloid leukemia, or stem-cell leukemia
• Any active infection requiring systemic therapy, including human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator (including but not limited to unstable angina, pre-existing liver disease, recurrent pancreatitis, uncontrolled diabetes, hypertriglyceridemia, pulmonary hypertension, or severe congestive heart failure (CHF) (New York Heart Association [NYHA] III-IV)
• Recurrent thrombosis, or non-central venous catheter associated thrombosis within 3mo prior to enrollment
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema
• Active CNS/leptomeningeal leukemia
• Severe comorbid conditions for which life expectancy would be < 6 months
• Patients with active (uncontrolled, metastatic) second malignancies are excluded
• History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
• Primary immunodeficiency or history of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to enrollment
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
• Live vaccine ≤ 4 weeks prior to enrollment
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 3 months after the last dose of trial treatment