Summary

for people ages up to 18 years (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Michelle Hermiston

Description

Summary

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.

Official Title

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)

Details

This study is part of an agreed Pediatric Investigation Plan (PIP). The single-arm study design includes r/r B-cell NHL subject population with poor prognosis, lack of approved effective therapies in this setting. Subject population will include aggressive subtypes of B-cell NHL and will be allowed to receive "bridging therapy" of investigator's choice After assessment of eligibility, subjects qualifying for the study will be enrolled and are allowed to start lymphodepleting chemotherapy as recommended in protocol after which a single dose of tisagenlecleucel product will be infused. The efficacy of tisagenlecleucel will be evaluated through the primary endpoint of Overall Response Rate (ORR) which includes complete response (CR) and partial response (PR) as determined by local assessment. Safety assessments will be conducted through the study completion.

Keywords

Non-Hodgkin Lymphoma Tisagenlecleucel relapsed/refractory B-cell non-Hodgkin lymphoma pediatric patients Burkitt's lymphoma (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 Lymphoma Lymphoma, Non-Hodgkin

Eligibility

You can join if…

Open to people ages up to 18 years

  • 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), gray zone lymphoma (GZL), and 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

  1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN) for age
  2. Total bilirubin <2 mg/dL (for Gilbert's Syndrome patients total bilirubin <4 mg/dL)
  3. Adequate pulmonary function
  4. Oxygen saturation of >91% on room air ii. No or mild dyspnea (≤Grade 1)
  5. Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.

You CAN'T join if...

  • 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Locations

  • UCSF Medical Center accepting new patients
    San Francisco California 94143 United States
  • Childrens Hospital Los Angeles accepting new patients
    Los Angeles California 90027 United States

Lead Scientist

  • Michelle Hermiston
    Associate Professor, Pediatrics. Authored (or co-authored) 74 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT03610724
Phase
Phase 2
Study Type
Interventional
Last Updated