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

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-15

Study Completion Date

2023-04-26

Brief Summary

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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.

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Detailed Description

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

Conditions

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Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tisagenlecleucel

Participants were infused once with CAR-positive viable T cells

Group Type EXPERIMENTAL

Tisagenlecleucel

Intervention Type BIOLOGICAL

Tisagenlecleucel was infused once as an intravenous infustion at a dose of either 0.2 to 5 x 106 CAR-positive viable T cells per kg body weight for subjects ≤ 50 kg or 0.1 to 2.5 x 108 CAR-positive viable T cells for subjects \> 50 kg.

lymphodepleting chemotherapy

Intervention Type DRUG

Prior to tisagenlecleucel infusion, each subject underwent lymphodepletion with recommended Fludarabine and cyclophosphamide (unless contra-indicated for subject)

Bridging Therapy

Intervention Type DRUG

Pre-treatment phase could also include bridging therapy of investigator's choice

Interventions

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Tisagenlecleucel

Tisagenlecleucel was infused once as an intravenous infustion at a dose of either 0.2 to 5 x 106 CAR-positive viable T cells per kg body weight for subjects ≤ 50 kg or 0.1 to 2.5 x 108 CAR-positive viable T cells for subjects \> 50 kg.

Intervention Type BIOLOGICAL

lymphodepleting chemotherapy

Prior to tisagenlecleucel infusion, each subject underwent lymphodepletion with recommended Fludarabine and cyclophosphamide (unless contra-indicated for subject)

Intervention Type DRUG

Bridging Therapy

Pre-treatment phase could also include bridging therapy of investigator's choice

Intervention Type DRUG

Other Intervention Names

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CTL019

Eligibility Criteria

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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.

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No