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JOURNAL ONKOLOGIE – STUDIE

Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia

Rekrutierend

NCT-Nummer:
NCT04925479

Studienbeginn:
Dezember 2021

Letztes Update:
03.05.2024

Wirkstoff:
Asciminib Pediatric formulation group, Asciminib Adult formulation group

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Philadelphia Chromosome

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Studienlocations
(3 von 34)

Novartis Investigative Site
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
33076 Bordeaux Cedex
FranceRekrutierend» Google-Maps
Novartis Investigative Site
232-8555 Yokohama-city
JapanRekrutierend» Google-Maps
Novartis Investigative Site
160 8582 Shinjuku-ku
JapanRekrutierend» Google-Maps
Novartis Investigative Site
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
3584 Utrecht
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
117198 Moscow
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
197022 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
10400 Bangkok
ThailandRekrutierend» Google-Maps
Novartis Investigative Site
40000 Khon Kaen
ThailandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

1. < 15% blasts in peripheral blood and bone marrow

2. < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow

3. < 20% basophils in the peripheral blood

4. 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

5. 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.

Studien-Rationale

Primary outcome:

1. 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).

2. 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).

3. 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).

4. 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).

5. 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).

Secondary outcome:

1. Hematologic responses (Time Frame - 52 weeks):
Complete hematological response will be defined as all of the following present for ≥ 4 weeks: WBC count < 10 x 10^9/L Platelet count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver

2. 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.

3. 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

Geprüfte Regime

  • Asciminib Pediatric formulation group (ABL001):
    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)
  • Asciminib Adult formulation group (ABL001):
    Asciminib Adult formulation group: 40 mg tablets BID, taken orally. 20 mg tablets BID, taken orally.

Quelle: ClinicalTrials.gov


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