- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04925479
Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia
A Multi-center, Open-label Study to Determine the Dose and Safety of Oral Asciminib in Pediatric Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP), Previously Treated With One or More Tyrosine Kinase Inhibitors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (PH+ CML-CP) previously treated with one or more Tyrosine kinase inhibitor (TKIs).
The primary objective of this study is to characterize the pharmacokinetic (PK) profile of asciminib in pediatric patients with the goal of identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
The pediatric formulation group will include at least 15 participants in each of the following two age categories: 1 to <12 years and 12 to <18 years; leading to at least 30 participants enrolled treated with the pediatric formulation. It will consist of a dose determination part (Part 1) and a cohort expansion (Part 2 BID regimen and Part 3 QD regimen).
In Part 1, 4-6 participants will be enrolled in order to obtain at least 4 participants evaluable for PK (these participants may be from either of the age categories described above). The initial starting dose will be based on body weight and will be administered BID with food.
Once the body weight adjusted dose has been determined in Part 1 of the study, the patients will be enrolled in Part 2 until at least 20 participants, including those who were included in Part 1, have been enrolled (10 per age group) in the pediatric formulation group. Once the interim safety and PK analysis 2 is completed for one of the age groups, the Part 3 QD regimen will open for the respective age group to enroll 10 patients (5 patients by age group).
Due to the fact that the pediatric formulation was in development and was not available, this study started with the recruitment of adolescent patients. These participants aged 14 to <18 years, weighing at least 40 kg receive the adult formulation at a flat dose of 40 mg BID under fasted conditions.
The total duration of the treatment period of the study will be 5 years (260 weeks). Participants who, according to Investigator's judgement, are benefiting from study treatment will remain on treatment up to the completion of the treatment period (Week 260/5 years). The primary analysis for the BID regimen is planned after all participants in Part 1 and 2 have completed at least 52 weeks of study treatment or discontinued earlier.
The primary analysis for combined regimen (BID+QD) is planned after all participants in Part 1, 2 and 3 have completed at least 52 weeks of study treatment or discontinued earlier.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Expanded Access
Contacts and Locations
Study Contact
- Name: Novartis Pharmaceuticals
- Phone Number: 1-888-669-6682
- Email: novartis.email@novartis.com
Study Contact Backup
- Name: Novartis Pharmaceuticals
- Phone Number: +41613241111
Study Locations
-
-
-
Beijing, China, 100044
- Recruiting
- Novartis Investigative Site
-
Shanghai, China, 200127
- Recruiting
- Novartis Investigative Site
-
Tianjin, China, 300020
- Recruiting
- Novartis Investigative Site
-
-
Zhejiang
-
Hangzhou, Zhejiang, China, 310005
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Bordeaux Cedex, France, 33076
- Recruiting
- Novartis Investigative Site
-
Lille, France, 59000
- Recruiting
- Novartis Investigative Site
-
Paris, France, 75019
- Recruiting
- Novartis Investigative Site
-
Poitiers, France, 86021
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Erlangen, Germany, 91054
- Recruiting
- Novartis Investigative Site
-
Essen, Germany, 45147
- Recruiting
- Novartis Investigative Site
-
Hamburg, Germany, 20246
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Athens, Greece, 115 27
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Budapest, Hungary, 1094
- Recruiting
- Novartis Investigative Site
-
-
-
-
GE
-
Genova, GE, Italy, 16147
- Recruiting
- Novartis Investigative Site
-
-
MB
-
Monza, MB, Italy, 20900
- Recruiting
- Novartis Investigative Site
-
-
TO
-
Torino, TO, Italy, 10126
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Osaka, Japan, 534-0021
- Recruiting
- Novartis Investigative Site
-
-
Kanagawa
-
Yokohama-city, Kanagawa, Japan, 232-8555
- Recruiting
- Novartis Investigative Site
-
-
Tokyo
-
Shinjuku-ku, Tokyo, Japan, 160 8582
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Seoul, Korea, Republic of, 03080
- Recruiting
- Novartis Investigative Site
-
-
Korea
-
Seoul, Korea, Korea, Republic of, 05505
- Recruiting
- Novartis Investigative Site
-
-
-
-
CS
-
Utrecht, CS, Netherlands, 3584
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Wrocław, Poland, 50367
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Moscow, Russian Federation, 117198
- Recruiting
- Novartis Investigative Site
-
Saint Petersburg, Russian Federation, 197022
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Bangkok, Thailand, 10400
- Recruiting
- Novartis Investigative Site
-
Khon Kaen, Thailand, 40000
- Recruiting
- Novartis Investigative Site
-
-
Chiangmai
-
Muang, Chiangmai, Thailand, 50200
- Recruiting
- Novartis Investigative Site
-
-
-
-
-
Istanbul, Turkey, 34093
- Recruiting
- Novartis Investigative Site
-
-
Gorukle
-
Bursa, Gorukle, Turkey, 16059
- Recruiting
- Novartis Investigative Site
-
-
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Recruiting
- Dana Farber Cancer Institute Dept.of DFCI
-
Principal Investigator:
- Jessica Pollard
-
Contact:
- Taylor Sorrentino
- Email: taylor_sorrentino@dfci.harvard.edu
-
-
New York
-
New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center- New York Presbyterian Herbert Irving Cancer Center
-
Contact:
- Phone Number: 212-305-9770
-
Principal Investigator:
- Nobuko Hijiya
-
-
Ohio
-
Cincinnati, Ohio, United States, 45229-3039
- Recruiting
- Cinn Children Hosp Medical Center
-
Principal Investigator:
- Benjamin Mizukawa
-
Contact:
- Jenni Ho
- Phone Number: 800-344-2462
- Email: jenni.ho@cchmc.org
-
-
Utah
-
Salt Lake City, Utah, United States, 84132
- Recruiting
- University of Utah Primary Childrens Hospital
-
Contact:
- Keeley Best
- Phone Number: 801-213-3599
- Email: Keeley.Best@imail2.org
-
Principal Investigator:
- Mallorie Heneghan
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female participants: Pediatric formulation group: ≥ 1 and less than 18 years of age at study entry. Adult formulation group: ≥ 14 and less than 18 years of age and body weight of ≥ 40 kg at study entry.
Participants with Ph+ CML-CP must meet all of the following laboratory values at the screening visit. In the case where bone marrow blast and promyelocyte counts are available, these will be accepted if done within 56 days prior to the screening visit, to avoid unnecessary repetition of this test.
- < 15% blasts in peripheral blood and bone marrow
- < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow
- < 20% basophils in the peripheral blood
- Neutrophils ≥ 1.5 x 10^9/L (or WBC ≥ 3 x 10^9/L if neutrophils are not available) and platelet count ≥ 100 x 10^9/L
- No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- Prior treatment with a minimum of one TKI
- Failure (adapted from the 2020 European Leukemia Net (ELN) Guidelines Hochhaus et al 2020 and 2013 ELN Guidelines Baccarani et al 2013) or intolerance to the most recent TKI therapy at the time of screening.
- Performance status: Karnofsky ≥ 50% for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age at the time of screening
- Participants must have adequate renal, hepatic, pancreatic and cardiac function
- Participants must have electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
- Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification.
Exclusion Criteria:
- Known presence of the T315I mutation prior to study entry.
- Known second chronic phase of CML after previous progression to AP/BC.
- Previous treatment with a hematopoietic stem-cell transplantation.
- Patient planning to undergo allogeneic hematopoietic stem cell transplantation.
- Cardiac or cardiac repolarization abnormality
- Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol
- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
- History of acute or chronic liver disease.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
- Pregnant or nursing (lactating) females.
Other protocol-defined inclusion/exclusion may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Asciminib
This arm consists of 2 groups:
|
Asciminib Adult formulation group: 40 mg tablets BID, taken orally. 20 mg tablets BID, taken orally.
Other Names:
Asciminib Pediatric formulation group: Mini-tablets will be supplied as size 0 capsules containing 1 mg mini-tablets, taken orally: 10 mg (10x 1 mg tablets in capsule) 15 mg (15x 1 mg tablets in capsule) 20 mg (20x 1 mg tablets in capsule) 30 mg (30x 1 mg tablets in capsule)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary Pharmacokinetic (PK) parameter: AUClast
Time Frame: 52 weeks
|
Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
|
52 weeks
|
Primary PK parameter: AUCtau
Time Frame: 52 weeks
|
Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
|
52 weeks
|
Secondary PK parameter: Cmax
Time Frame: 52 weeks
|
Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
|
52 weeks
|
Secondary PK parameter: Tmax
Time Frame: 52 weeks
|
Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
|
52 weeks
|
Secondary PK parameter: Ctrough
Time Frame: 52 weeks
|
Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hematologic responses
Time Frame: 52 weeks
|
Complete hematological response will be defined as all of the following present for ≥ 4 weeks:
|
52 weeks
|
Molecular responses
Time Frame: 52 weeks
|
To assess pharmacodynamic markers of asciminib's anti-leukemic activity.
Molecular response will be assessed by Breakpoint Cluster Region gene-Abelson proto-oncogene (BCR-ABL) 1 level.
|
52 weeks
|
Questionnaire on acceptability and palatability after first dose, 4 and 52 weeks
Time Frame: after first dose at Week 1 Day 1, 4 weeks, 52 weeks
|
To assess acceptability and palatability of the pediatric formulation
|
after first dose at Week 1 Day 1, 4 weeks, 52 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Chromosome Aberrations
- Translocation, Genetic
- Chronic Disease
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Philadelphia Chromosome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Micronutrients
- Protein Kinase Inhibitors
- Vitamins
- Vitamin B Complex
- Tyrosine Kinase Inhibitors
- Niacinamide
- Asciminib
Other Study ID Numbers
- CABL001I12201
- 2021-001286-20 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD 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 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.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myeloid Leukemia, Philadelphia Positive
-
University of ConnecticutCompletedStudy Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic PhaseLeukemia,Myeloid, Chronic | Leukemia,Myeloid,Philadelphia-PositiveUnited States
-
Novartis PharmaceuticalsCompletedPhiladelphia Chromosome Positive CMLUnited States, Germany, Italy, France
-
Bristol-Myers SquibbCompletedChronic Myeloid Leukemia | Philadelphia-Positive Myeloid LeukemiaBelgium, Netherlands, Spain, United States, Italy, Canada, France, Germany, Peru, Singapore, United Kingdom, Australia, Sweden, Finland, Israel, Ireland, Denmark, Korea, Republic of, Norway, Austria, South Africa, Switzerland
-
Bristol-Myers SquibbCompletedChronic Myeloid Leukemia | Philadelphia-Positive Myeloid LeukemiaBelgium, Spain, United States, Italy, Argentina, Brazil, Canada, Germany, Peru, Puerto Rico, Singapore, South Africa, Taiwan, United Kingdom, Australia, France, Philippines, Sweden, Thailand, Russian Federation, China, Poland, Finland, Isra... and more
-
Novartis PharmaceuticalsCompletedPhiladelphia Chromosome Positive Chronic Myelogenous LeukemiaGermany, Canada, France, Spain, Italy
-
Bristol-Myers SquibbCompletedMyeloid Leukemia, ChronicJapan
-
Hikma Pharmaceuticals LLCCompletedPhiladelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic PhaseEgypt
-
OHSU Knight Cancer InstituteAriad PharmaceuticalsNo longer availableChronic Myeloid Leukemia | Philadelphia Chromosome Positive (Ph+) LeukemiasUnited States
-
PfizerCompletedPhiladelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML)Singapore
-
Renato MelaragnoUnknownChronic Myeloid Leukemia (CML) With Philadelphia Chromosome-positive (Ph+)Brazil
Clinical Trials on Asciminib Adult formulation group
-
ActelionCompleted
-
AbbVieCompletedHepatitis C Virus (HCV)United States, Belgium, Canada, Germany, Japan, Puerto Rico, Russian Federation, Spain, United Kingdom
-
Shanghai BDgene Co., Ltd.Eye & ENT Hospital of Fudan UniversityCompletedCornea | Herpes Simplex Virus Infection | Viral Keratitis | Blindness EyeChina
-
The Royal Ottawa Mental Health CentreEnrolling by invitationParaphilias and Paraphilic DisordersCanada
-
Idorsia Pharmaceuticals Ltd.CompletedSafety, Tolerability, Pharmacokinetics and PharmacodynamicsFrance
-
Max Zeller Soehne AGCompleted
-
Peter TonnUniversitätsklinikum Hamburg-EppendorfRecruiting
-
Sinovac Biotech Co., LtdCompleted
-
Riphah International UniversityCompleted