Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients (BIANCA)
Non-Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for Non-Hodgkin Lymphoma focused on measuring Tisagenlecleucel, relapsed/refractory B-cell non-Hodgkin lymphoma, pediatric patients, Burkitt lymphoma (BL), Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), follicular lymphoma (FL), leukapheresis, lymphodepleting chemotherapy (LD), NHL
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes; Burkitt lymphoma/ Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
- Patients <25 years of age and weighing at least 6 kg at the time of screening
- Patients who have relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant) or are primary refractory (have not achieved a CR or PR after the first line of therapy)
- Measurable disease by radiological criteria in all patients at the time of screening. Patients with Burkitt leukemia who don't meet radiological criteria must have bone marrow involvement of >25% by local assessment of bone marrow aspirate and/or biopsy.
- Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status ≥60.
Adequate bone marrow reserve without transfusions (transfusion >2 weeks prior to laboratory assessment is allowed) defined as:
- Absolute neutrophil count (ANC) >1000/mm3
- Platelets ≥50000//mm3
- Hemoglobin ≥8.0 g/dl
Adequate organ function defined as:
a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine (mg/dL) Age Male Female
1 to <2 years 0.6 0.6 2 to <6 years 0.8 0.8 6 to <10 years 1.0 1.0 10 to <13 years 1.2 1.2 13 to <16 years 1.5 1.4
≥16 years 1.7 1.4
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN) for age
- Total bilirubin <2 mg/dL (for Gilbert's Syndrome patients total bilirubin <4 mg/dL)
- Adequate pulmonary function
i. Oxygen saturation of >91% on room air ii. No or mild dyspnea (≤Grade 1)
- Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.
Exclusion Criteria:
- Prior gene therapy or engineered T cell therapy.
- Prior treatment with any anti-CD19 therapy.
- Allogeneic hematopoietic stem cell transplant (HSCT) <3 months prior to screening and ≤4 months prior to infusion.
- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) in patients who received prior allogeneic HSCT.
- Prior diagnosis of malignancy other than study indication, and not disease free for 5 years.
- Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
- Presence of active hepatitis B or C as indicated by serology.
- Human Immunodeficiency Virus (HIV) positive test.
- Active neurological autoimmune or inflammatory disorders not related to B cell NHL (eg: Guillain-Barre syndrome, Amyotrophic Lateral Sclerosis)
- Active central nervous system (CNS) involvement by malignancy.
- Patients with B-cell NHL in the context of post-transplant lymphoproliferative disorders (PTLD) associated lymphomas.
Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Childrens Hospital Los Angeles
- UCSF Medical Center
- Johns Hopkins Oncology Center ORA
- Dana Farber Cancer Institute Dept.of DFCI
- Memorial Sloan Kettering Cancer Center MSKCC (8)
- Cinn Children Hosp Medical Center
- The Childrens Hospital of Philadelphia Drug Shipment
- University of Texas Southwestern Medical Center .
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Kyoto University Hospital
- Novartis Investigative Site
- Prinses Maxima Centrum voor Kinderoncologie
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Experimental
Tisagenlecleucel
CAR-positive viable T cells infusion