Acute Lymphoblastic Leukemia
Conditions
Interventions
KTE-X19 treatment consists of Conditioning Chemotherapy of 900 mg/m^2
cyclophosphamide & 25 mg/m^2 fludarabine for 3 x days followed by a target dose
of 2x10E6 CAR T cells/kg, 1x10E6 CAR T cells/kg
Sponsors
Kite Pharma Inc.
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: ALL Cohort 101. Relapsed or refractory B-precursor ALL defined as one of the following: - Primary refractory disease - Any relapse within 18 months after first diagnosis - Relapsed or refractory disease after 2 or more lines of systemic therapy - 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. Disease burden defined as at least 1 of the following: -Morphological disease in the bone marrow (>5% blasts) -MRD positive (threshold 10-4 by flow or PCR) 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 = 21 years and weight >= 6 kg. Note: Subjects with a weight of >= 6 kg to = 90% CD19 positive. NHL Cohort 301. Histologically confirmed aggressive B cell NHL: - DLBCL not otherwise specified - Primary mediastinal large B-cell lymphoma (including Mediastinal gray zone lymphoma) - Burkitt lymphoma, Burkitt-like lymphoma and Unclassified B-cell lymphoma intermediate between DLBCL and Burkitt lymphoma 302. Relapsed or refractory disease defined as 1 or more of the following: - Primary refractory disease - Relapsed or refractory disease after 2 or more lines of systemic therapy - Relapsed or refractory disease after autologous /allogeneic SCT provided subject is at least 100 days from SCT at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment 303. Subjects must have received adequate prior therapy including at a minimum all of the following: - Anti-CD20 monoclonal antibody, unless the investigator determines that the tumor is CD20 negative - An anthracycline-containing chemotherapy regimen 304. At least 1 measurable lesion according to the revised International Pediatric Non-Hodgkin Lymphoma Staging System {Rosolen 2015}. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. 305. Magnetic resonance imaging (MRI) of the brain showing no evidence of CNS lymphoma 308. Age or = 6kg Note: Subjects with a weight of >= 6 kg to or = 16 years at the time of assent/consent) performance status > or = 80 at screening 106. and 310. ANC > or = 500/uL unless, in the opinion of the PI, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy 107. and 311. Platelet count > or = 50,000/uL unless, in the opinion of the PI, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy 108.
Exclusion criteria
Exclusion criteria: ALL Cohort 201. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis 202. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years 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 with neurological symptoms defined as detectable cerebrospinal blast cells in a sample of CSF with =5/µL in CSF with presence of lymphoblasts with or without neurologic symptoms. c. Presence of CNS 2 disease defined as WBC <5/µL in CSF with presence of lymphoblasts and with neurologic symptoms (see note below for further clarification). Note: Neurologic symptoms may include but are not limited to cranial nerve palsy (if not explained by extracranial tumor) and clinical cord compression. [Subjects with CNS-1 (no detectable lymphoblasts in the CSF) and those with CNS 2 without clinically evident neurological changes are eligible to participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs). Phase 2: ALL Cohort: Overall complete remission rate (CR + CRi) per independent review. All subjects who do not meet the criteria for CR or CRi by the analysis data cutoff date will be considered non-responders for the overall complete remission rate evaluation. NHL Cohort: ORR per investigator assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: - Overall complete remission rate (CR + CRi) per investigator assessment - Duration of Remission (DOR) in the ALL and NHL cohort - Minimal Residual Disease (MRD) negative rate in ALL cohort - Allogeneic SCT rate - Overall survival (OS) in the ALL and NHL cohort - Relapsed-free Survival (RFS) in ALL cohort - Incidence of AEs and Common Terminology Criteria for Adverse Events (CTCAE) grade changes in safety laboratory values in the ALL and NHL cohort - Incidence of anti-KTE-X19 antibodies in the ALL and NHL cohort - Progression free survival in the NHL cohort | — |
Countries
Netherlands
Outcome results
None listed