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Tisagenlecleucel

Antineoplastic Agents, Immunological

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

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

CTL019

Novartis Pharmaceuticals

Colleen Quinn

Matthew Kutny

Dresden Whitehead

Dana Salzberg

Anna Pawlowska

Lee Chen

Emily Hsieh

Eunice Kim

Satiro De Oliveira

Tina Templeman

Van Huynh

Alexandria Lim

Kara Davis

Reuven Schore

Joanna Gallacher

Deepakbabu Chellapandian

Sarah Votaw

Muna Qayed

Jennifer Pencek

April Rahrig

Clare Twist

Eileen Phifer

Timothy A Driscoll

Adam Nelson

Christine Phillips

Nycole Ferguson

Bill Chang

Aakruti Sharma

Shannon Maude

Taryn Harris

Samuel John

Mark De Hoyos

Amanda Lipsitt

Jenny Weiland

Christian Capitini

Tara Murphy

Julie-An Talano

R. Pieters

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.

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

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

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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.

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.

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

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.

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

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.

Absolute lymphocyte CD19 count of \<50/uL

Success in manufacturing of tisagenlecleucel dose for patients who are ≥1 year and \<3 years as respective time points.

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).

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).

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

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

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

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).

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

Impact of immunogenicity on clinical response

Transgene concentration as detected by qPCR in target tissue

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

Relationship between B-cell recovery and transgene levels

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

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

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

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

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

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

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

Clinical response summarized by quartile of administered doses

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

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)

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)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients	NCT03876769	B-Cell Acute Ly...	CTL019	1 Year - 25 Years	Novartis
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients	NCT03876769	B-Cell Acute Ly...	CTL019	1 Year - 25 Years	Novartis

Spots Global Cancer Trial Database for positive at the end of consolidation (eoc)