Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL (ELIANA)

Condition(s)
Leukemia

Age Group
0-9 years 10-17 years 18-26 years

Phase(s)
2

Biological treatment cell Biological
CTL019
Trial Summary & Details
Ages: 3 Years to 30 Years
Condition: Childhood Acute Lymphoblastic Leukemia

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.

The study will have 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.

Results & References
  • Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.

    BACKGROUND:
    In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

    METHODS:
    We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.

    RESULTS:
    For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported.

    CONCLUSIONS:
    In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849)

Status
Active not recruiting
Location(s)
Childrens Hospital Los Angeles, Los Angeles, CA
Stanford University Medical Center - Stanford, CA
Children's Healthcare of Atlanta, Atlanta, GA
University of Michigan, Ann Arbor, MI
University of Minnesota, Minneapolis, MN
Mercy Children's Kansas University, Kansas City, MO
Duke University Medical Center, Durham, NC
Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Oregon Health & Science University Doernbecher Children's Hosp., Portland, OR
The Childrens Hospital of Philadelphia (CHOP), Philadelphia, PA
Children's Medical Center of Dallas, Dallas, TX
University of Utah, Salt Lake City, UT
University of Wisconsin Hospital and Clinics, Madison, WI
Novartis Investigative Site, Parkville, Victoria, Australia
Novartis Investigative Site, Wien, Austria
Novartis Investigative Site, Gent, Belgium
Novartis Investigative Site, Toronto, Ontario, Canada
Novartis Investigative Site, Montreal, Quebec, Canada
Novartis Investigative Site, Paris Cedex 10, Cedex 10, France
Novartis Investigative Site, Paris, France
Novartis Investigative Site, Frankfurt, Germany
Novartis Investigative Site, Monza, MB, Italy
Novartis Investigative Site, Sakyo-ku, Kyoto, Japan
Novartis Investigative Site, Oslo, Norway
Novartis Investigative Site, Esplugues de Llobregat, Barcelona, Spain

Sponsor/Collaborators:
Novartis Pharmaceuticals
Contact
Not available.