A Phase II, single arm, multicenter open label trial to determine the safety and efficacy of tisagenlecleucel in pediatric patients with relapsed or refractory mature B-cell non-Hodgkin lymphoma (NHL) (BIANCA)

Protocol # :
Non-Hodgkin Lymphoma
Disease Sites
Non-Hodgkin's Lymphoma
Principal Investigator
Davies, Kimberly, J.

Trial Description

The purpose of the study was to assess the efficacy and safety of tisagenlecleucel in
pediatric, adolescent and young adult patients with relapsed/refractory B-cell non-Hodgkin
lymphoma (r/r B-NHL) including Burkitt Lymphoma and Burkitt Leukemia.

For pediatric patients who have r/r B-NHL including Burkitt Lymphoma and Burkitt Leukemia,
survival rates are dismal, only ~20-50% subjects are alive at 2 years with overall response
rate (ORR) of 20-30% after conventional salvage chemotherapy.

Eligibility Requirements

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:

1. Absolute neutrophil count (ANC) >1000/mm3

2. Platelets ≥50000//mm3

3. Hemoglobin ≥8.0 g/dl

- Adequate organ function defined as:

1. 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

2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the
upper limit of normal (ULN) for age

3. Total bilirubin <2 mg/dL (for Gilbert's Syndrome patients total bilirubin <4

4. 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

- 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.