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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03610724




Registration number
NCT03610724
Ethics application status
Date submitted
13/07/2018
Date registered
1/08/2018

Titles & IDs
Public title
Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients
Scientific 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)
Secondary ID [1] 0 0
2017-005019-15
Secondary ID [2] 0 0
CCTL019C2202
Universal Trial Number (UTN)
Trial acronym
BIANCA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Tisagenlecleucel
Treatment: Drugs - lymphodepleting chemotherapy
Treatment: Drugs - Bridging Therapy

Experimental: Tisagenlecleucel - Participants were infused once with CAR-positive viable T cells


Treatment: Other: 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.

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

Treatment: Drugs: Bridging Therapy
Pre-treatment phase could also include bridging therapy of investigator's choice
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) as Determined by Local Investigator
Timepoint [1] 0 0
6 months post-tisagenlecleucel infusion
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Secondary outcome [2] 0 0
Event Free Survival (EFS)
Timepoint [2] 0 0
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Secondary outcome [3] 0 0
Relapse Free Survival (RFS)
Timepoint [3] 0 0
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Secondary outcome [6] 0 0
Cellular Kinetics Parameter: Cmax
Timepoint [6] 0 0
Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48
Secondary outcome [7] 0 0
Cellular Kinetics Parameter: Tmax
Timepoint [7] 0 0
Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48
Secondary outcome [8] 0 0
Cellular Kinetics Parameter: AUC0-28d
Timepoint [8] 0 0
0 to 28 days
Secondary outcome [9] 0 0
Cellular Kinetics Parameter: Clast
Timepoint [9] 0 0
Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48
Secondary outcome [10] 0 0
Cellular Kinetics Parameter: Tlast
Timepoint [10] 0 0
Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48
Secondary outcome [11] 0 0
Levels of Pre-existing and Treatment Induced Humoral Immunogenicity and Cellular Immunogenicity Against Tisagenlecleucel Cellular Kinetics, Safety and Efficacy
Timepoint [11] 0 0
Until disease progression or through study completion, up to 4 years
Secondary outcome [12] 0 0
Percentage of Participants Who Proceeded to Stem Cell Transplant (SCT) After Tisagenlecleucel Infusion
Timepoint [12] 0 0
Through study completion, up to 4 years
Secondary outcome [13] 0 0
Maximum Positive Predictive Value (PPV)
Timepoint [13] 0 0
Through study completion, up to 4 years

Eligibility
Key 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.
Minimum age
No limit
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/04/2023
Sample size
Target
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Austria
State/province [8] 0 0
Wien
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Denmark
State/province [10] 0 0
Copenhagen
Country [11] 0 0
Finland
State/province [11] 0 0
Helsinki
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Villejuif
Country [14] 0 0
Germany
State/province [14] 0 0
Muenster
Country [15] 0 0
Italy
State/province [15] 0 0
MB
Country [16] 0 0
Italy
State/province [16] 0 0
RM
Country [17] 0 0
Japan
State/province [17] 0 0
Kyoto
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Netherlands
State/province [19] 0 0
CS
Country [20] 0 0
Norway
State/province [20] 0 0
Oslo
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
United Kingdom
State/province [23] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03610724