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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02435849




Registration number
NCT02435849
Ethics application status
Date submitted
16/04/2015
Date registered
6/05/2015

Titles & IDs
Public title
Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients
Scientific title
A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
2013-003205-25
Secondary ID [2] 0 0
CCTL019B2202
Universal Trial Number (UTN)
Trial acronym
ELIANA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
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 - CTL019

Experimental: Single dose of CTL019 - Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (CTL019).


Treatment: Other: CTL019
Tisagenlecleucel was administered as a single iv infusion. Dose: 2.0 to 5.0x10\^6 tisagenlecleucel per kg body weight (for patients = 50 kg) or 1.0 to 2.5x10\^8 tisagenlecleucel (for patients \>50 kg).

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment.
Timepoint [1] 0 0
during the 3 months after tisagenlecleucel administration
Secondary outcome [1] 0 0
Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary)
Timepoint [1] 0 0
3 months after tisagenlecleucel administration
Secondary outcome [2] 0 0
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary)
Timepoint [2] 0 0
3 months after tisagenlecleucel administration
Secondary outcome [3] 0 0
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary)
Timepoint [3] 0 0
3 months after tisagenlecleucel administration
Secondary outcome [4] 0 0
Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT)
Timepoint [4] 0 0
6 months after tisagenlecleucel administration
Secondary outcome [5] 0 0
Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion
Timepoint [6] 0 0
up to 6 months
Secondary outcome [7] 0 0
Duration of Remission (DOR)
Timepoint [7] 0 0
60 months
Secondary outcome [8] 0 0
Site of Involvement of Subsequent Relapse
Timepoint [8] 0 0
60 months
Secondary outcome [9] 0 0
Relapse-free Survival Per IRC Assessment
Timepoint [9] 0 0
60 months
Secondary outcome [10] 0 0
Event-free Survival Per IRC Assessment
Timepoint [10] 0 0
60 months
Secondary outcome [11] 0 0
Overall Survival (OS)
Timepoint [11] 0 0
60 months
Secondary outcome [12] 0 0
Percentage of Participants Attaining CR or CRi at Day 28 +/- 4 Days Post Tisagenlecleucel (CTL019) Infusion by IRC Assessment
Timepoint [12] 0 0
1 month
Secondary outcome [13] 0 0
Response as a Function of Baseline Tumor Burden (Tumor Load) in Main Cohort Only
Timepoint [13] 0 0
3 months
Secondary outcome [14] 0 0
Bone Marrow MRD Status by Flow Cytometry Per IRC Assessment
Timepoint [14] 0 0
28 days
Secondary outcome [15] 0 0
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood by Day 28 Response by Independent Review Committee (IRC) Assessment
Timepoint [15] 0 0
Month 60
Secondary outcome [16] 0 0
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow by Day 28 Response by IRC Assessment
Timepoint [16] 0 0
Month 6
Secondary outcome [17] 0 0
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Peripheral Blood by Day 28 Disease Response Per IRC Assessment
Timepoint [17] 0 0
Month 60
Secondary outcome [18] 0 0
Expression of Tisagenlecleucel (CTL019) Detected by Flow Cytometry in Bone Marrow by Day 28 Response by IRC Assessment
Timepoint [18] 0 0
Month 6
Secondary outcome [19] 0 0
Pharmacokinetics (PK) Parameter: Cmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Timepoint [19] 0 0
60 months
Secondary outcome [20] 0 0
Pharmacokinetics (PK) Parameter: Tmax by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Timepoint [20] 0 0
60 months
Secondary outcome [21] 0 0
Pharmacokinetics (PK) Parameter: AUCs by qPCR in Peripheral Blood, by Day 28 Disease Response by IRC
Timepoint [21] 0 0
0 to 84 days after infusion
Secondary outcome [22] 0 0
Persistence of Tisagenlecleucel (CTL019) in Blood, Bone Marrow and CSF if Available, by qPCR, by Day 28 Response by IRC
Timepoint [22] 0 0
60 months
Secondary outcome [23] 0 0
Prevalence and Incidence of Immunogenicity to Tisagenlecleucel (CTL019)
Timepoint [23] 0 0
At any time post-baseline, up to a max. of 60 months
Secondary outcome [24] 0 0
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by PedsQL Questionnaire
Timepoint [24] 0 0
Month 3, M6, M12, M24, M60
Secondary outcome [25] 0 0
Effects of CTL019 Therapy on Patient Reported Outcomes as Measured by EQ-5D Questionnaire
Timepoint [25] 0 0
Month 60
Secondary outcome [26] 0 0
Develop a Score Utilizing Clinical and Biomarker Data and Assess Its Ability for Early Prediction of Cytokine Release Syndrome (CRS)
Timepoint [26] 0 0
3 months
Secondary outcome [27] 0 0
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (C Reactive Protein & Ferritin)
Timepoint [27] 0 0
Maximum post-baseline (approx. 60 months)
Secondary outcome [28] 0 0
Frequent Monitoring of Concentrations of Soluble Immune Factors in Blood (All Other Inflammatory Markers)
Timepoint [28] 0 0
Maximum post-baseline (approx. 60 months)
Secondary outcome [29] 0 0
Percentage Change From Baseline of Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion
Timepoint [29] 0 0
Month 3, Month 12, Maximum post-baseline (approx. 60 months)
Secondary outcome [30] 0 0
Percentage of Participants With Overall Remission Rate (ORR) - From Fraunhofer Institute Manufacturing Facility
Timepoint [30] 0 0
60 months
Secondary outcome [31] 0 0
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From Fraunhofer Institute Manufacturing Facility as Per IRC
Timepoint [31] 0 0
3 months
Secondary outcome [32] 0 0
Tisagenlecleucel Transgene Levels by qPCR in Peripheral Blood - Tisagenlecleucel Manufactured From Fraunhofer Institute
Timepoint [32] 0 0
Month 60
Secondary outcome [33] 0 0
Tisagenlecleucel Transgene Levels by qPCR in Bone Marrow - Tisagenlecleucel Manufactured From Fraunhofer Institute
Timepoint [33] 0 0
Month 3

Eligibility
Key inclusion criteria
1. Relapsed or refractory pediatric B-cell ALL
2. Adequate organ function
3. For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry.
4. Bone marrow with = 5% lymphoblasts by morphologic assessment at screening.
5. Life expectancy > 12 weeks.
6. Karnofsky (age =16 years) or Lansky (age < 16 years) performance status = 50 at screening
7. Signed written informed consent and assent forms
8. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product
9. Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.
10. Cohort 1 only:

1. First relapse AND hypodiploid cytogenetics OR
2. First relapse AND t(17;19) with defined TCF3-HLF fusion OR
3. First relapse with any cytogenetics provided the relapse occurred = 36 months of initial diagnosis AND MRD at end of reinduction therapy is =0.01% by flow cytometry (local assessment)
Minimum age
No limit
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Isolated extra-medullary disease relapse
2. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
5. Treatment with any prior gene therapy product
6. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
8. Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
9. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).
10. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.
11. Patient has an investigational medicinal product within the last 30 days prior to screening.
12. Pregnant or nursing (lactating) women.
13. Women of child-bearing potential, defined as physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception for at least 12 months after the CTL019 infusion and after CAR T-cells are no longer present by qPCR on two consecutive tests
14. Sexually active males must use a condom during intercourse at least 12 months after the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive tests

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 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
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Austria
State/province [11] 0 0
Wien
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
France
State/province [15] 0 0
Cedex 10
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Germany
State/province [17] 0 0
Frankfurt
Country [18] 0 0
Italy
State/province [18] 0 0
MB
Country [19] 0 0
Japan
State/province [19] 0 0
Kyoto
Country [20] 0 0
Norway
State/province [20] 0 0
Oslo
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona

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 review 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 availability is according to the criteria and 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.