Acute Lymphoblastic LeukemiaPhase 3NCT03123939
Phase III B in Acute Lymphoblastic Leukemia
A Phase 3 study testing CTL019 in people with Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
Trial summary
This is a single arm, open-label, multi-center, phase III B study to determine the safety and efficacy of CTL019 in pediatric/young adult patients with r/r B-cell Acute Lymphoblastic Leukemia (ALL). Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- CTL019
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 11 sitesin 9 countries
- Study dates
- 24 Apr 2017to 13 Oct 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Relapsed or refractory B-cell ALL in pediatric or young adult patients:
- Second or greater bone marrow relapse.
- Any bone marrow relapse after allogeneic SCT and must be ≥ 4 months from SCT at the time of CTL019 infusion OR
- 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
- Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
- Ineligible for allogeneic SCT
Show all 37Show fewer
- For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of program entry.For relapsed or refractory patients previously treated with blinatumomab, CD19 tumor expression must be demonstrated (via flow cytometry) at Screening.
- Adequate organ function defined as:
- A serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL). Age Male Female: to < 2 years 0.6 0.6; 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.
- ALT ≤ 5 times the upper limit of normal (ULN) for age.
- Bilirubin < 2.0 mg/dL.
- Minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air.
- Left Ventricular Shortening Fraction ≥ 28% by echocardiogram, or Left Ventricular Ejection Fraction ≥ 45% by echocardiogram or Multiple Uptake Gated Acquisition (MUGA).
- Life expectancy > 12 weeks.
- Age less than 26 at the time of screening.
- Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening.
- Patients previously treated with blinatumomab who have detectable leukemia and documented CD19+ expression (via flow cytometry) and confirmed absence of CD19- leukemic blasts at Screening may be included. In this case, at least 1 week washout period must be applied from last dose of blinatumomab to start of leukapheresis. Patients previously treated with blinatumomab with no detectable MRD (i.e. MRD negative demonstrated by leukemic blasts < 0.01%) will be excluded.
- Must have a leukapheresis product of non-mobilized cells received and accepted by the manufacturing site.
- Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are not eligible. However, such patients with other forms of CNS-3 leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least 3 months prior to CTL019 infusion. Patients must have no acute/ongoing neurologic toxicity > Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 3 months.
- Exclusion criteria Isolated extra-medullary disease relapse. Concomitant genetic syndromes associated with bone marrow failure states: 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 surface immunoglobulin (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.
- Prior treatment with any gene therapy product. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab 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 GVHD. Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening Investigational medicinal product within the last 30 days prior to screening. Pregnant or nursing women.Women of child-bearing potential 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:
- Steroids: Therapeutic systemic doses of steroids must be stopped > 72 hours prior to CTL019 infusion.
- Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed > 6 weeks prior to CTL019 infusion.
- GVHD therapies: Any systemic drug used for GVHD must be stopped > 4 weeks prior to CTL019 infusion to confirm that GVHD recurrence is not observed.
- Chemotherapy:
- TKIs and hydroxyurea must be stopped > 72 hours prior to CTL019 infusion.
- must be stopped > 1 week prior to CTL019 infusion: vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non pegylated).
- must be stopped > 2 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide, methotrexate ≥ 25 mg/m2).
- Pegylated-asparaginase must be stopped > 4 weeks prior to CTL019 infusion.
- CNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate).
- Radiotherapy
- Non-CNS site of radiation must be completed > 2 weeks prior to CTL019 infusion.
- CNS directed radiation must be completed > 8 weeks prior to CTL019 infusion.
- Anti T-cell antibodies: Administration of any T cell lytic or toxic antibody (e.g. alemtuzumab) within 8 weeks prior to CTL019 is prohibited Other protocol-defined inclusion/exclusion may apply
Who cannot join
None listed.
Trial locations and contacts
11 sites in 9 countries.
11 sites in 9 countries
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1C5
Novartis Investigative Site
Toronto, Ontario, M5G 1X8
France2 sites
Novartis Investigative Site
Paris, 75019
Novartis Investigative Site
Paris, 75475
Spain1 site
Novartis Investigative Site
Esplugues de Llobregat, Barcelona, 08950
About this study
Official title: Phase IIIb Study for Relapsed/Refractory Pediatric/Young Adult Acute Lymphoblastic Leukemia Patients to be Treated With CTL019
This is a single arm, open-label, multi-center, phase III B study to determine the safety and efficacy of CTL019 in pediatric/young adult patients with r/r B-cell Acute Lymphoblastic Leukemia (ALL).
Read the detailed description
This was a single-arm, multi-centeric Phase IIIb study provided pediatric/young adult patients with r/r B-cell ALL the opportunity to be treated with CTL019. The main purpose of this study was to assess the safety of CTL019 for up to 12 months after the CTL019 infusion. The study had the following sequential phases for all patients: Screening including leukapheresis, Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy), Treatment and Follow-up, and Long-Term Follow-Up (LTFU). The end of study (EOS) was defined as the last patient's last visit, which was the last patient's Month 12 evaluation, or the time of premature withdrawal. All patients were followed in this study for up to 12 months after the CTL019 infusion.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- CTL019
- Keywords
- ALL, Acute Lymphoblastic Leukemia, CTL019, relapsed/refractory pediatric/young adult
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTL019Biological
CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg)
| Study group | Role | What they receive |
|---|---|---|
| CTL019 | Experimental | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) Receives: Biological: CTL019 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months
Measured: From CTL019 infusion until end of study, up to 12 months
Secondary outcomes (22)
Overall Remission Rate (ORR)
ORR is defined as the proportion of participants with a best overall disease response of Complete remission (CR) or CR with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until Month 6.
Measured: From CTL019 infusion until Month 6
Number of Participants Who Achieved CR or CRi at Month 6 Without Stem Cell Transplantation (SCT)
Proportion of participants who achieved CR or CRi at Month 6 without stem cell transplantation between CTL019 infusion and Month 6 response assessment
Measured: Month 6
Number of Participants Who Achieved CR or CRi and Then Proceeded to Stem Cell Transplantation (SCT) While in Remission Before Month 6 Assessment
Proportion of participants who achieved CR or CRi and then proceeded to stem cell transplantation while in remission prior to Month 6 response assessment.
Measured: From CTL019 infusion until Month 6
Duration of Response (DOR)
DOR is the duration of remission from the date when the response criteria of CR or CRi was first met post CTL019 infusion to the date of relapse or death due to acute lymphoblastic leukemia (ALL), whichever occured first.
Measured: Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Relapse-free Survival (RFS)
RFS is measured by the time from achievement of CR or CRi whichever occured first post CTL019 infusion, to relapse or death due to any cause during CR or CRi.
Measured: Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Event-free Survival (EFS)
EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure.
Measured: Actual reported Time Frame: up to 15.1 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Overall Survival (OS)
OS is the time from date of CTL019 infusion to the date of death due to any reason
Measured: Actual reported Time Frame: up to 24.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Number of Participants Who Attained CR or CRi at Day 28
Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion.
Measured: Day 28
Number of Participants Who Attained CR or CRi at Day 28 by Baseline Bone Marrow Tumor Burden
Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion by baseline bone marrow tumor burden.
Measured: Day 28
Bone Marrow Minimum Residual Disease (MRD) Status by Flow Cytometry on Day 28 Post CTL019 Infusion
MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (flow cytometry).
Measured: Enrollment/Pre-chemotherapy and Day 28
Bone Marrow Minimum Residual Disease (MRD) Status by qPCR on Day 28 Post CTL019 Infusion
MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (qPCR).
Measured: Enrollment/Pre-chemotherapy and Day 28
Incidence of Immunogenicity Against CTL019 - Humoral Immunogenicity
The humoral immunogenicity assessment included evaluation of pre-existing (pre-treatment) and post-treatment anti-CTL019 antibodies to examine the incidence of immunogenicity with treatment.
Measured: Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12
Incidence of Immunogenicity Against CTL019 - Cellular Immunogenicity
The cellular immunogenicity assessment included percentage of CD4+ and CD8+ T- cells specific for CTL019.
Measured: Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12
AUC0-28d: PK Parameters for CTL019 by qPCR
Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 28 after single dose administration as measured by qPCR.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28
AUC0-84d: PK Parameters for CTL019 by qPCR
Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 84 after single dose administration as measured by qPCR.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 and 84
Cmax: PK Parameters for CTL019 by qPCR
The maximum (peak) observed in peripheral blood drug concentration after single dose administration
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Clast: PK Parameters for CTL019 by qPCR
The last observed in peripheral blood drug concentration after single dose administration.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Tmax: PK Parameters for CTL019 by qPCR
The time to reach maximum (peak) peripheral blood drug concentration after single dose administration.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
T1/2: PK Parameters for CTL019 by qPCR
The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Tlast: PK Parameters for CTL019 by qPCR
The time to reach the last observed quantifiable concentration in peripheral blood after single dose administration.
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
AUC0-28d by Maximum Cytokine Release Syndrome (CRS) Grade
AUC0-28d from time zero to Day 28 after single dose administration as measured by qPCR. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
- - Mild reaction
- - Moderate reaction
- - More severe reaction
- - Life-threatening complications
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28
Cmax by Maximum Cytokine Release Syndrome (CRS) Grade
The maximum (peak) observed in peripheral blood drug concentration after single dose administration. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
- - Mild reaction
- - Moderate reaction
- - More severe reaction
- - Life-threatening complications
Measured: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start24 Apr 2017
- Primary completion13 Oct 2020
- Study completion13 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03123939
- Sponsor's protocol ID
- CCTL019B2001X
- Other IDs
- 2016-001991-31, 2016
- Status last verified
- Jun 2021
- First submitted
- 13 Apr 2017
- Last updated
- 21 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022 Jun;36(6):1508-1515. doi: 10.1038/s41375-022-01550-z. Epub 2022 Apr 14.
PubMed 35422096
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIIb Study for Relapsed/Refractory Pediatric/Young Adult Acute Lymphoblastic Leukemia Patients to be Treated With CTL019
- ClinicalTrials.gov ID
- NCT03123939
- Acronym / sponsor ID
- CCTL019B2001X
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- ALL, Acute Lymphoblastic Leukemia, CTL019, relapsed/refractory pediatric/young adult
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 13 Oct 2020 (actual)
- Study completion
- 13 Oct 2020 (actual)
- First posted
- 21 Apr 2017 (actual)
- Results
- Posted 21 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, open-label, multi-center, phase III B study to determine the safety and efficacy of CTL019 in pediatric/young adult patients with r/r B-cell Acute Lymphoblastic Leukemia (ALL).
Detailed description
This was a single-arm, multi-centeric Phase IIIb study provided pediatric/young adult patients with r/r B-cell ALL the opportunity to be treated with CTL019. The main purpose of this study was to assess the safety of CTL019 for up to 12 months after the CTL019 infusion. The study had the following sequential phases for all patients: Screening including leukapheresis, Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy), Treatment and Follow-up, and Long-Term Follow-Up (LTFU). The end of study (EOS) was defined as the last patient's last visit, which was the last patient's Month 12 evaluation, or the time of premature withdrawal. All patients were followed in this study for up to 12 months after the CTL019 infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CTL019 | Experimental | Biological: CTL019CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (37 listed)
- Second or greater bone marrow relapse.
- Any bone marrow relapse after allogeneic SCT and must be ≥ 4 months from SCT at the time of CTL019 infusion OR
- 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
- Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
- Ineligible for allogeneic SCT
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CTL019CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) | Biological | CTL019 |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From CTL019 infusion until end of study, up to 12 months
Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months
22 secondary outcomes
Overall Remission Rate (ORR)
Time frame: From CTL019 infusion until Month 6
Number of Participants Who Achieved CR or CRi at Month 6 Without Stem Cell Transplantation (SCT)
Time frame: Month 6
Number of Participants Who Achieved CR or CRi and Then Proceeded to Stem Cell Transplantation (SCT) While in Remission Before Month 6 Assessment
Time frame: From CTL019 infusion until Month 6
Duration of Response (DOR)
Time frame: Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Relapse-free Survival (RFS)
Time frame: Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Event-free Survival (EFS)
Time frame: Actual reported Time Frame: up to 15.1 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Overall Survival (OS)
Time frame: Actual reported Time Frame: up to 24.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)
Number of Participants Who Attained CR or CRi at Day 28
Time frame: Day 28
Number of Participants Who Attained CR or CRi at Day 28 by Baseline Bone Marrow Tumor Burden
Time frame: Day 28
Bone Marrow Minimum Residual Disease (MRD) Status by Flow Cytometry on Day 28 Post CTL019 Infusion
Time frame: Enrollment/Pre-chemotherapy and Day 28
Bone Marrow Minimum Residual Disease (MRD) Status by qPCR on Day 28 Post CTL019 Infusion
Time frame: Enrollment/Pre-chemotherapy and Day 28
Incidence of Immunogenicity Against CTL019 - Humoral Immunogenicity
Time frame: Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12
Incidence of Immunogenicity Against CTL019 - Cellular Immunogenicity
Time frame: Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12
AUC0-28d: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28
AUC0-84d: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 and 84
Cmax: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Clast: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Tmax: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
T1/2: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Tlast: PK Parameters for CTL019 by qPCR
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
AUC0-28d by Maximum Cytokine Release Syndrome (CRS) Grade
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28
Cmax by Maximum Cytokine Release Syndrome (CRS) Grade
Time frame: Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35422096Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022 Jun;36(6):1508-1515. doi: 10.1038/s41375-022-01550-z. Epub 2022 Apr 14.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CTL019 in people with Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Canada, France, Austria, Belgium, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From CTL019 infusion until end of study, up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03123939, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2021.