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)
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
mg/dL)
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 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.