The Safety and Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients

Why are we doing this research?

The purpose of the study is to assess the efficacy and safety of tisagenlecleucel in children and adolescents with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). For pediatric patients who have r/r B-NHL, 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.

CCTL019C2202: A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Safety and Efficacy of Tisagenlecleucel in Pediatric Subjects With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma (NHL)

Who can participate?

Inclusion Criteria:

  • Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes:
    • Burkitt Lymphoma (BL)
    • Diffuse large B-cell lymphoma (DLBCL)
    • Primary mediastinal B-cell lymphoma (PMBCL)
    • Grey zone lymphoma (GZL)
    • Follicular lymphoma (FL)
    • Note: Patients with bone marrow involvement of >25% lymphoma cells by bone marrow biopsy/aspirate evaluation, will be excluded. Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
  • Patients <18 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.
  • 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
    • Absolute lymphocyte count (ALC) >300/mm3
    • Absolute number of CD3+ T cells >150/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
  • 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.
  • Active, uncontrolled infection despite treatment at screening.
  • Presence of active or prior 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.

Ages

  • Up to 18 Years

Conditions

  • Lymphoma Non Hodgkin Relapse

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org