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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02435849
Ethics application status
Date submitted
16/04/2015
Date registered
6/05/2015
Date last updated
12/09/2018

Titles & IDs
Public title
Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL
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:
Lymphoblastic Leukemia 0 0
Acute 0 0
Childhood 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
Other interventions - Single dose of CTL019

Experimental: Single dose of CTL019 - 2 to 5 x 10(6) autologous CTL019 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion.


Other interventions: Single dose of CTL019
2 to 5 x 10(6) autologous CTL019 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion.

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

Outcomes
Primary outcome [1] 0 0
Overall remission rate (ORR) = CR + CRi - Efficacy of CTL019 therapy as measured by overall remission rate during the 3 months after CTL019 administration, which includes CR and CR with incomplete blood count recovery (CRi) as determined by IRC assessment.
Timepoint [1] 0 0
After manufactured pts have received CTL019 infuson and completed 3 months from study day 1 infusion or discontinued earlier
Secondary outcome [1] 0 0
Percentage of patients who achieve best overall response (BOR) or CR or CRi with an MRD negative bone marrow by central analysis using qPCR
Timepoint [1] 0 0
3 months
Secondary outcome [2] 0 0
Percentage of patients who achieve CR or CRi at month 6 without SCT between CTL019 infusion and Month 6 response assessment.
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Duration of remission (DOR)
Timepoint [3] 0 0
60 months
Secondary outcome [4] 0 0
Percentage of patients who achieve CR or CRi with minimal residual disease negative bone marrow
Timepoint [4] 0 0
3 months
Secondary outcome [5] 0 0
Relapse-free survival
Timepoint [5] 0 0
60 months
Secondary outcome [6] 0 0
Event-free survival
Timepoint [6] 0 0
60 months
Secondary outcome [7] 0 0
Overall survival
Timepoint [7] 0 0
60 months
Secondary outcome [8] 0 0
Response at Day 28 +/- 4 days
Timepoint [8] 0 0
1 month
Secondary outcome [9] 0 0
Impact of baseline tumor burden on response
Timepoint [9] 0 0
60 months
Secondary outcome [10] 0 0
Percentage of patient who achieve CR or CRi and then proceed to SCT while in remission before Month 6 response assessment
Timepoint [10] 0 0
6 months
Secondary outcome [11] 0 0
Quality of response using MRD disease assessments before treatment at day 28 +/-4 days after treatment using central assessments by qPCR and before SCT by local assessment (flow or PCR)
Timepoint [11] 0 0
60 months
Secondary outcome [12] 0 0
Safety of CTL019 therapy
Timepoint [12] 0 0
60 months
Secondary outcome [13] 0 0
Characterize in vivo cellular PK profile of CTL019 cells in target tissues
Timepoint [13] 0 0
60 months
Secondary outcome [14] 0 0
Prevalence and incidence of immunogenicity to CTL019
Timepoint [14] 0 0
60 months
Secondary outcome [15] 0 0
Effects of CTL019 therapy on Patient Reported Outcomes
Timepoint [15] 0 0
60 months
Secondary outcome [16] 0 0
Derivation of a score to predict cytokine release syndrome
Timepoint [16] 0 0
3 months
Secondary outcome [17] 0 0
Describe the profile of soluable immune factors that may be key to cytokine release syndrome
Timepoint [17] 0 0
6 months
Secondary outcome [18] 0 0
Describe levels of B and T cells (blood and bone marrow) prior to and following CTL019 infusion for safety monitoring
Timepoint [18] 0 0
3 months

Eligibility
Key inclusion criteria
- Relapsed or refractory pediatric B-cell ALL.

1. 2nd or greater Bone Marrow (BM) relapse OR.

2. Any BM relapse after allogeneic stem cell transplantation (SCT) and must be = 6
months from SCT at the time of CTL019 infusion OR.

3. Primary refractory as defined by not achieving a CR after 2 cycles of a standard
chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1
cycle of standard chemotherapy for relapsed leukemia OR.

4. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI),
or if TKI therapy is contraindicated OR.

5. Ineligible for allogeneic SCT.

- For relapsed patients, documentation of CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study entry.

- Adequate organ function defined as:

1. Renal function defined as:

A serum creatinine based on age/gender 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. Alanine Aminotransferase (ALT) = 5 times the upper limit of normal (ULN) for age.

3. Bilirubin < 2.0 mg/dL.

4. Must have a minimum level of pulmonary reserve as = Grade 1 dyspnea and pulse
oxygenation > 91% on room air.

5. Left Ventricular Shortening Fraction (LVSF) = 28% confirmed by echocardiogram
(ECHO), or Left Ventricular Ejection Fraction (LVEF) = 45% confirmed by
echocardiogram or Multiple Uptake Gated Acquisition (MUGA).

- Bone marrow with = 5% lymphoblasts by morphologic assessment at screening.

- Life expectancy > 12 weeks.

- Age 3 at the time of screening to age 21 at the time of initial diagnosis

- Karnofsky (age = 16 years) or Lansky (age < 16 years) performance status = 50 at
screening.

- Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.
Minimum age
3 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Isolated extra-medullary disease relapse

- 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.

- 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)

- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
intent and with no evidence of active disease

- Treatment with any prior gene therapy product

- Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
therapy

- Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),
or any uncontrolled infection at screening

- Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening

- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).

- Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.

- Patient has an investigational medicinal product within the last 30 days prior to
screening.

- Pregnant or nursing women.

- Women of child-bearing potential (defined as all women physiologically capable of
becoming pregnant) and all male participants, unless they are using highly effective
methods of contraception for a period of 1 year after the CTL019 infusion.

- The following medications are excluded:

1. Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to
CTL019 infusion. However, the following physiological replacement doses of
steroids are allowed:

< 12 mg/m2/day hydrocortisone or equivalent

2. Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be
completed > 6 weeks prior to CTL019 infusion

3. GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CTL019
infusion (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs,
mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as
anti-CD20 (rituximab), anti-TNF, anti-IL6 or anti-IL6R)

4. Chemotherapy:

The following drugs must be stopped > 1 week prior to CTL019 infusion and should
not be administered concomitantly or following lymphodepleting chemotherapy:
hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25
mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non-pegylated)

The following drugs must be stopped >2 weeks prior to CTL019 infusion:

salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2,
anthracyclines, cyclophosphamide), excluding the required lymphodepleting
chemotherapy drugs Pegylated-asparaginase must be stopped > 4 weeks prior to
CTL019 infusion

5. CNS disease prophylaxis:

CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g.
intrathecal methotrexate)

- Anti T-cell therapy: Administration of any T cell or toxic agent is strongly
discouraged since residual lytic levels may destroy the infused CTL019 cell or prevent
their in vivo expansion.

Other protocol-defined inclusion/exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Active, not recruiting
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
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Austria
State/province [13] 0 0
Wien
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Cedex 10
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt
Country [20] 0 0
Italy
State/province [20] 0 0
MB
Country [21] 0 0
Japan
State/province [21] 0 0
Kyoto
Country [22] 0 0
Norway
State/province [22] 0 0
Oslo
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and
safety of CTL019 in pediatric patients with r/r B-cell ALL.
Trial website
https://clinicaltrials.gov/show/NCT02435849
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

Summary results
Other publications