Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients (ELIANA)
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|ClinicalTrials.gov Identifier: NCT02435849|
Recruitment Status : Completed
First Posted : May 6, 2015
Results First Posted : November 22, 2021
Last Update Posted : February 2, 2023
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|Condition or disease||Intervention/treatment||Phase|
|B-cell Acute Lymphoblastic Leukemia||Biological: CTL019||Phase 2|
This was a initially a one cohort, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL. This main cohort completed enrollment. Two new cohorts were added via an amendment, Cohort 1 for high risk B-cell ALL patients at first relapse, and Cohort 2 for feasibility and safety of CTL019 in high risk B-cell ALL in patients that relapsed <6 months post allo-HSCT. Due to lack of recruitment, both of these cohorts have halted recruitment. This decision was not related to any safety issue.
The study had the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and Survival Follow-up. The total duration of the study is 5 years from CTL019 cell infusion.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||97 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Actual Study Start Date :||April 8, 2015|
|Actual Primary Completion Date :||January 21, 2020|
|Actual Study Completion Date :||November 17, 2022|
Experimental: Single dose of CTL019
Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (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).
- Percentage of Participants With Overall Remission Rate (ORR) as Determined by IRC Assessment. [ Time Frame: during the 3 months after tisagenlecleucel administration ]Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee ( IRC) assessment.
- Percentage of Patients Who Achieve Best Overall Response (BOR) or CR or CRi With an MRD Negative Bone Marrow by Central Analysis Using qPCR [ Time Frame: 3 months ]
- Percentage of Patients Who Achieve CR or CRi at Month 6 Without SCT Between CTL019 Infusion and Month 6 Response Assessment. [ Time Frame: 6 months ]
- Duration of Remission (DOR) [ Time Frame: 60 months ]
- Percentage of Patients Who Achieve CR or CRi With Minimal Residual Disease Negative Bone Marrow [ Time Frame: 3 months ]
- Relapse-free Survival [ Time Frame: 60 months ]
- Event-free Survival [ Time Frame: 60 months ]
- Overall Survival [ Time Frame: 60 months ]
- Response at Day 28 +/- 4 Days [ Time Frame: 1 month ]
- Impact of Baseline Tumor Burden on Response [ Time Frame: 60 months ]
- Percentage of Patient Who Achieve CR or CRi and Then Proceed to SCT While in Remission Before Month 6 Response Assessment [ Time Frame: 6 months ]
- 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) [ Time Frame: 60 months ]
- Safety of CTL019 Therapy [ Time Frame: 60 months ]
- Characterize in Vivo Cellular PK Profile of CTL019 Cells in Target Tissues [ Time Frame: 60 months ]
- Prevalence and Incidence of Immunogenicity to CTL019 [ Time Frame: 60 months ]
- Effects of CTL019 Therapy on Patient Reported Outcomes [ Time Frame: 60 months ]
- Derivation of a Score to Predict Cytokine Release Syndrome [ Time Frame: 3 months ]
- Describe the Profile of Soluble Immune Factors That May be Key to Cytokine Release Syndrome [ Time Frame: 6 months ]
- Describe Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion for Safety Monitoring [ Time Frame: 3 months ]
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|Ages Eligible for Study:||up to 25 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Relapsed or refractory pediatric B-cell ALL
- Adequate organ function
- For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- Life expectancy > 12 weeks.
- Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening
- Signed written informed consent and assent forms
- Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product
- Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.
Cohort 1 only:
- First relapse AND hypodiploid cytogenetics OR
- First relapse AND t(17;19) with defined TCF3-HLF fusion OR
- 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)
- 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 (lactating) women.
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435849
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|
Documents provided by Novartis ( Novartis Pharmaceuticals ):
|Responsible Party:||Novartis Pharmaceuticals|
|Other Study ID Numbers:||
2013-003205-25 ( EudraCT Number )
|First Posted:||May 6, 2015 Key Record Dates|
|Results First Posted:||November 22, 2021|
|Last Update Posted:||February 2, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||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
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
r/r B-cell ALL
high risk B-cell ALL at first relapse
high risk B-cell ALL that relapsed < 6 months post allo-HSCT
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Immunological