Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm, Residual

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

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

Children's Oncology Group

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Disease Progression

Disease Attributes

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Immunomodulating Agents

For patients with advanced NSCLC who have long-term benefit (PFS 12 months) after first-line immunotherapy

High-depth sequencing method is used to detecting ctDNA.

ctDNA detection

Chunhong Hu, professor

Fang Wu, professor

This study aims to explore the correlation of circulating tumor DNA(ctDNA) and the risk of progression in patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months)

Evidence suggests that circulating tumor DNA (ctDNA) analysis can noninvasively identify minimal residual disease (MRD) in clinical oncology. The researches will be sharply increased about ctDNA potential clinical application in the near future. In the early stage of NSCLC, ctDNA has been indicated to identify those at high risk of recurrence after radical surgery. And this study will focus on those patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months). 10ml plasma will be collected every three months until disease progression to interrogate ctDNA by high-depth panel sequencing, exploring its prediction value about the risk of progression. Meanwhile, the investigators would like to explore the lead time of detectable ctDNA before regular imaging finding.

ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC

A Multicenter, Prospective Clinical Study of Circulating Tumor DNA Analysis to Monitor the Risk of Progression After Long-term Benefit to First-line Immunotherapy in Patients With Advanced NSCLC (CR1STAL)

Time from the beginning of first-line immunotherapy to the first progression(PD) in patients with advanced NSCLC.

The correlation of ctDNA and risk of progression during the erolled observation process

Lead time defined as the interval between ctDNA detection and imaging of progression.

the incidence of adverse events during the whole observation time

Overall survival (OS) defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

Sun Yat-sen University

First Affiliated Hospital Xi'an Jiaotong University

Fujian Cancer Hospital

Third Affiliated Hospital of Third Military Medical University

Xiangya Hospital of Central South University

Qinghai Province Tumor Hospital

Wuhan Union Hospital, China

Zhejiang Provincial People's Hospital

Hunan Province Tumor Hospital

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Second Affiliated Hospital, School of Medicine, Zhejiang University

Zhejiang Cancer Hospital

The First Affiliated Hospital of Guangzhou Medical University

Inner Mongolia People's Hospital

Guizhou Provincial People's Hospital

The Third Xiangya Hospital of Central South University

Yueyang Central Hospital

ZhuZhou Central Hospital

Zhangjiajie Affiliated Hospital of Hunan Normal University

Loudi Central Hospital

Chang Sha First Hospital

Fang Wu

Associate Professor

Digestive System Diseases

Recurrence

Cholangiocarcinoma

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Cancer

Biliary Tract Cancer

Patients with stage I-III biliary tract cancers eligible for curative surgical resection

No intervention

Xiangcheng Li, PhD

Xiaofeng Chen, PhD

A substantial proporation of patients with biliary tract malignancies still experience disease recurrence after curative resection. ctDNA-based minimal residual disease (MRD) method has been widely used to monitor postoperative recurrence in solid cancers, but few studies have been reported in biliary tract cancers.

The present clinical trial aims to elucidate the correlation between the postoperative ctDNA status and the prognosis of patients with biliary tract cancers, and evaluate whether ctDNA could better predict patients' recurrence and guide clinical practice.

ctDNA Detection of MRD in Predicting Postoperative Recurrence in Biliary Tract Cancers：A Multicenter Prospective Trial

The primary endpoint for this study is Relapse-free survival (RFS), which will be assessed using RECIST version 1.1.

The First Affiliated Hospital with Nanjing Medical University

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Folic Acid

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Patients will receive mFOLFOXIRI chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy

Patients will receive mFOLFOX6 chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy

mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most

mFOLFOXIRI

mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC	NCT05198154	Advanced Lung N...	ctDNA detection	18 Years - 75 Years	Second Xiangya Hospital of Central South University
ctDNA Detection of MRD in Predicting Postoperative Recurrence in Biliary Tract Cancers：A Multicenter Prospective Trial	NCT05743959	Biliary Tract C...	No intervention	18 Years -	The First Affiliated Hospital with Nanjing Medical University
Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD)	NCT05427669	Colorectal Canc...	mFOLFOXIRI mFOLFOX6	18 Years - 70 Years	Sun Yat-sen University
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
Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer	NCT04842006	Colorectal Canc...	Total neoadjuva... Minimal residua... Long radiation ...	18 Years - 100 Years	Helsinki University Central Hospital
Non-invasive MRD Assessment in Multiple Myeloma	NCT05625971	Myeloma	MRD Assessment	18 Years -	Columbia University
Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer	NCT04842006	Colorectal Canc...	Total neoadjuva... Minimal residua... Long radiation ...	18 Years - 100 Years	Helsinki University Central Hospital

Spots Global Cancer Trial Database for minimal residual disease (mrd)