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Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients (ELIANA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02435849
Recruitment Status : Completed
First Posted : May 6, 2015
Results First Posted : November 22, 2021
Last Update Posted : February 2, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
B-cell Acute Lymphoblastic Leukemia Biological: CTL019 Phase 2

Detailed Description:

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Single dose of CTL019
Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (CTL019).
 Biological: 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).


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Duration of Remission (DOR) [ Time Frame: 60 months ]
  4. Percentage of Patients Who Achieve CR or CRi With Minimal Residual Disease Negative Bone Marrow [ Time Frame: 3 months ]
  5. Relapse-free Survival [ Time Frame: 60 months ]
  6. Event-free Survival [ Time Frame: 60 months ]
  7. Overall Survival [ Time Frame: 60 months ]
  8. Response at Day 28 +/- 4 Days [ Time Frame: 1 month ]
  9. Impact of Baseline Tumor Burden on Response [ Time Frame: 60 months ]
  10. 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 ]
  11. 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 ]
  12. Safety of CTL019 Therapy [ Time Frame: 60 months ]
  13. Characterize in Vivo Cellular PK Profile of CTL019 Cells in Target Tissues [ Time Frame: 60 months ]
  14. Prevalence and Incidence of Immunogenicity to CTL019 [ Time Frame: 60 months ]
  15. Effects of CTL019 Therapy on Patient Reported Outcomes [ Time Frame: 60 months ]
  16. Derivation of a Score to Predict Cytokine Release Syndrome [ Time Frame: 3 months ]
  17. Describe the Profile of Soluble Immune Factors That May be Key to Cytokine Release Syndrome [ Time Frame: 6 months ]
  18. Describe Levels of B and T Cells (Blood and Bone Marrow) Prior to and Following CTL019 Infusion for Safety Monitoring [ Time Frame: 3 months ]

Eligibility Criteria
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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] March 21, 2019
Statistical Analysis Plan  [PDF] May 27, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02435849    
Other Study ID Numbers: CCTL019B2202
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
Plan Description:

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
URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Pediatric
ALL
Cell therapy
Lymphoblastic Leukemia
Acute
High Risk
Childhood
 CTL019
tisagenlecleucel
Pediatric patients
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
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Tisagenlecleucel
Antineoplastic Agents, Immunological
Antineoplastic Agents