Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)
B-Cell Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for B-Cell Acute Lymphoblastic Leukemia focused on measuring CTL019, Kymriah, B-Cell Acute Lymphoblastic Leukemia, ALL, tisagenlecleucel, HR B-ALL EOC MRD, Minimal Residual Disease (MRD), Positive at the End of Consolidation (EOC)
Eligibility Criteria
Inclusion Criteria:
- CD19 expressing B-cell Acute Lymphoblastic Leukemia
- De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
- Age 1 to 25 years at the time of screening
- Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
Adequate organ function during the screening period:
A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL)
E. Adequate pulmonary function defined as:
- no or mild dyspnea (≤ Grade 1)
- oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
- Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.
Exclusion Criteria:
- M3 marrow at the completion of 1st line induction therapy
- M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening.
- Philadelphia chromosome positive ALL
- Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
- Prior tyrosine kinase inhibitor therapy
- Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
- Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
- Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy
Other protocol-defined inclusion/exclusion may apply.
Sites / Locations
- Children s Hospital of AlabamaRecruiting
- Phoenix Children's HospitalRecruiting
- City of Hope National MedicalRecruiting
- Childrens Hospital Los Angeles SC CTL019Recruiting
- Mattel Childrens Hospital UCLARecruiting
- Children's Hospital of Orange County CHOC Children'sRecruiting
- Rady Children s Hospital CTBM100C2401Recruiting
- UCSF Medical Center .Recruiting
- Stanford Universtiy Medical Center .Recruiting
- Childrens Hospital ColoradoRecruiting
- Yale School of MedicineRecruiting
- Childrens National HospitalRecruiting
- Johns Hopkins All childrensRecruiting
- Children's Healthcare of Atlanta Emory University IRBRecruiting
- Ann and Robert H Lurie Childrens Hospital of ChicagoRecruiting
- University of ChicagoRecruiting
- James Whitcomb Riley Hospital for ChildrenRecruiting
- Norton Children s HospitalRecruiting
- Johns Hopkins Oncology Center Cancer Research BuildingRecruiting
- Dana Farber Cancer Institute Dept.of DFCIRecruiting
- University of MichiganRecruiting
- University of Minnesota CAEB071B2201Recruiting
- University of Mississippi Medical Center Childrens Hospital .Recruiting
- Children s Mercy HospitalRecruiting
- St. Louis University/Cardinal Glennon Children's HospitalRecruiting
- Washington University CTBM100C2412Recruiting
- University of Nebraska Medical CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Roswell Park Cancer InstituteRecruiting
- Cohen Children's Medical Center of New York
- Memorial Sloan Kettering Cancer CenterRecruiting
- Columbia University Medical Center OncologyRecruiting
- Duke University Medical Center .Recruiting
- Cinn Children Hosp Medical CenterRecruiting
- Univ Hospital - Cleveland/Rainbow Babies and Children's Hosp Pediatric NephrologyRecruiting
- Cleveland ClinicRecruiting
- Nationwide Childrens Hospital suite T6BRecruiting
- Oregon Health and Science University .Recruiting
- Penn State Childrens HospitalRecruiting
- The Childrens Hospital of Philadelphia Div Gastroint., Hepat. & Nutr.Recruiting
- Medical Uni of South Carolina Medical Univ of SCRecruiting
- Monroe Carell Jr Childrens Hospital at VanderbiltRecruiting
- University of Texas Southwestern Medical CenterRecruiting
- Texas Children's Cancer and Hematology CenterRecruiting
- Methodist Children's Hospital .Recruiting
- University of Utah Clinical Trials Office .Recruiting
- Children's Hospital of Richmond at VCU Pediatric Hematology OncologyRecruiting
- University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping AddressRecruiting
- Childrens Hospital of WisconsinRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative Site
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Prinses Maxima Centrum voor KinderoncologieRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Experimental
Single dose of CTL019
Based on the subject's weight one of two possible dose ranges will be prepared for the subject: Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight OR Subjects > 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells