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NCT Number: NCT03876769

Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, patient will have assessments performed more frequently in the first month and then at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Efficacy and safety will be assessed at study visits and as clinically indicated throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up safety will continue under a separate protocol per health authority guidelines.

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Key information

Conditions

B-cell Acute Lymphoblastic Leukemia Burkitt Lymphoma DNA Virus Infections Epstein-Barr Virus Infections Hemic and Lymphatic Diseases Herpesviridae Infections Immune System Diseases Immunoproliferative Disorders Infections Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasm, Residual Neoplasms Neoplasms by Histologic Type Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Tumor Virus Infections Virus Diseases

Age range

1 year–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Ghent, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • CD19 expressing B-cell Acute Lymphoblastic Leukemia
  • De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
  • Age 1 to 25 years at the time of screening
  • Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
  • Adequate organ function during the screening period:

A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL)

E. Adequate pulmonary function defined as:

  • no or mild dyspnea (≤ Grade 1)
  • oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
  • Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.

Exclusion criteria

  • M3 marrow at the completion of 1st line induction therapy
  • M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening.
  • Philadelphia chromosome positive ALL
  • Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
  • Prior tyrosine kinase inhibitor therapy
  • Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
  • Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
  • Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy

Other protocol-defined inclusion/exclusion may apply.

Treatment and study plan

CTL019

Biological

Based on the subject's weight, one of two possible dose ranges will be prepared for the subject:

Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight

OR

Subjects > 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Primary outcomes

  1. Disease Free Survival (DFS) rate without censoring for new anticancer therapy, including Stem Cell Transplantation (SCT) while in remission

    Time frame: 5 years after tisagenlecleucel infusion

    DFS is defined as the time from the date of tisagenlecleucel infusion to the date of the first documented morphological relapse, occurrence of secondary malignancy or death due to any cause.

  2. Overall Survival (OS) rate

    Time frame: 4 years after tisagenlecleucel

    OS is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any reason.

Secondary outcomes

  1. Percentage of participants who are disease free without allogeneic stem cell transplant (SCT)

    Time frame: 12 months after last infusion

    Minimal Residual Disease (MRD) negative remission (complete remission (CR) or Complete remission with incomplete blood count recovery CRi)) at Month 12 without SCT after tisagenlecleucel infusion.

  2. DFS rate with censoring for new anticancer therapy, including SCT, while in remission

    Time frame: 5 years

    Assessing the effect of tisagenlecleucel on DFS if new anticancer therapy is not available.

  3. Percentage of participants achieving MRD negative CR or CRi at Month 3

    Time frame: 3 months after the tisagenlecleucel infusion.

    Assessing the percentage of participants who achieved MRD negative complete response (CR) or Complete remission with incomplete blood count recovery (CRi) status as determined by central laboratory using multi-parameter flow cytometry.

  4. Pediatric Quality of Life (PedsQL)

    Time frame: 5 years

    Patient reported outcome to assess quality of life in patients aged 8 and above. The 23 items PedQL (Pediatrics Quality of Life Inventory) measure core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning.

    Items measured include 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items).

    Each item is measured on a 5 point Likert scale with 0 indicating "never" and 4 indicating "almost always".

    The Likert scores are reversed scored and linearly transform to a 0-100 scale with 0=100, 1-75, 2=50, 5=25, and 4=0. A higher score indicates better health-related quality of life (HRQoL).

  5. European Quality of Life 5 dimensions (EQ-5D-3L & EQ-5D-Y))

    Time frame: 5 years

    Patient reported outcome to assess health status in patients aged 8 and above. The EQ-5D (European Quality of Life -5 Dimensions) measures a wide range of health conditions and treatments; it is composed of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and a visual analogue scale (EQ-visual analogue scale [EQ-VAS]) that records the patient's self-rated overall health state.

    Respondents rate each of these 5 dimensions from "no problem", "some problem," or "extreme problem".

    The EQ-VAS records the respondents' self-related health on a vertical, visual analogue scale. The range for EQ-VAS is from 0 (=the worst health you can imagine) to 100 (=the best health you can imagine).

  6. Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: Detection test

    Time frame: 5 years

    Speed of performance (mean of the log10 transformed reaction times for correct responses)

  7. Impact of tisagenlecleucel on cognitive functioning usingComputerized neurocognitive assessment: Identification test

    Time frame: 5 years

    This test measures the speed of performance (mean of the log10 transformed reaction times for correct responses)

  8. Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: Groton Maze Learning test

    Time frame: 5 years

    This test looks at the total number of errors made in attempting to learn the hidden pathways during a single session.

  9. Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: One Back test

    Time frame: 5 years

    This test measures the accuracy of performance (arcsine transformation of the square root of the percentage of correct responses). The test also measures the speed of performance (mean of the log10 transformed reaction times for correct responses).

  10. Impact of tisagenlecleucel on cognitive functioning usingComputerized neurocognitive assessment: One card learning test

    Time frame: 5 years

    This test measures the accuracy of performance (arcsine transformation of the square root of the proportion of correct responses).

  11. Percentage of participants with pre-existing antibodies

    Time frame: 8 years

    Prevalence of immunogenicity

  12. Percentage of participants with anti-m CAR19 antibodies post infusion with tisagenlecleucel and % of patients without measureable anti-mCAR19 antibodies

    Time frame: 8 years

    Incidence of immunogenicity

  13. Percentage of patients that have measureable anti-mCAR19 antibodies above patient specific cut-point (reported as a %) pre and post tisagenlecleucel infusion categorized by Day 28 response

    Time frame: 8 years

    Impact of immunogenicity on clinical response

  14. tisagenlecleucel transgene concentration

    Time frame: 8 years

    Transgene concentration as detected by qPCR in target tissue

  15. Expression of tisagenlecleucel

    Time frame: 8 years

    Summary of tisagenlecleucel CAR-positive viable T cells measured by flow cytometry in target tissue

  16. Persistence of CAR (reported as copies/ug) categorized by the time to B-cell recovery (recovery < 3 months, >3 months to < 6months, > 6 months)

    Time frame: 8 years

    Relationship between B-cell recovery and transgene levels

  17. Cmax; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/μg)

  18. Tmax; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)

  19. AUC0-29d and 84d; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The AUC from time zero to day 29 and 84 or other disease assessment days, in peripheral blood (% or copies/μg x days )

  20. AUC0-Tmax; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The AUC from time zero to Tmax in peripheral blood (% or copies/μg x days)

  21. T1/2; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood

  22. Clast; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The last observed quantifiable concentration in peripheral blood (% or copies/μg)

  23. Tlast; cellular kinetic parameter of tisagenlecleucel

    Time frame: 8 years

    The time of last observed quantifiable concentration in peripheral blood (days)

  24. Impact of tisagenlecleucel dose on day 29 response

    Time frame: 8 years

    Clinical response summarized by quartile of administered doses

  25. AUC 0 - 29d; cellular kinetic parameter of tisagenlecleucel

    Time frame: Day 29

    Impact of tisagenlecleucel exposure on day 29 response; The AUC from time zero to day 29 in peripheral blood (% or copies/μg x days )

  26. Cmax: cellular kinetic parameter of tisagenlecleucel

    Time frame: Day 29

    Impact of tisagenlecleucel exposure on day 29 response; The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/μg)

  27. Tmax: cellular kinetic parameter of tisagenlecleucel

    Time frame: Day 29

    Impact of tisagenlecleucel exposure on day 29 response; The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)

  28. T1/2: cellular kinetic parameter of tisagenlecleucel

    Time frame: Day 29

    Impact of tisagenlecleucel exposure on day 29 response; The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Collaborators

  • Children's Oncology Group

Registry information

Official study title

A Phase II Trial of Tisagenlecleucel in First-line High-risk (HR) Pediatric and Young Adult Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL) Who Are Minimal Residual Disease (MRD) Positive at the End of Consolidation (EOC) Therapy

Acronym: CASSIOPEIA

Important dates

Study start
2019
Primary completion
2027
Study completion
2027
First posted
Mar 15, 2019
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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