Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients

Status: Active

Description

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.

Eligibility Criteria

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), 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
  • 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.
  • 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.

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222
Email: cancertrials@ucsf.edu

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Approved
Name Not Available

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Boston Children's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Name Not Available

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Marcella West Aguilar
Phone: 214-648-1479
Email: marcella.aguilar@utsouthwestern.edu

Utah

Salt Lake City
Primary Children's Hospital
Status: In review
Name Not Available

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Jenny Lynn Weiland
Phone: 608-890-8070
Email: jlweiland@pediatrics.wisc.edu

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Novartis Pharmaceuticals Corporation

Trial IDs

Primary ID CCTL019C2202
Secondary IDs NCI-2019-01191, 2017-005019-15
Clinicaltrials.gov ID NCT03610724