Trial Title:
Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation
NCT ID:
NCT06427811
Condition:
Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Asciminib
Conditions: Keywords:
ABL001
Asciminib
Ph+ CML-CP
T315I mutation
Ph+ CML-CP without T315I mutation
Ph+ CML-CP with the T315I mutation
Myelogenous
Chronic
Chronic Myeloid Leukemia
Ph1 Positive Myeloid Leukemia
Philadelphia Positive Myeloid Leukemia
BCR-ABL Positive
Post-authorization Interventional Study
Tyrosine Kinase Inhibitors
TKI
Chronic Leukemia
Ph1 Positive Leukemia
Without T315I mutation
with the T315I mutation
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Asciminib
Description:
Film-coated tablets with 40 mg dose strength taken orally
Arm group label:
Asciminib 200 mg
Arm group label:
Asciminib 80 mg
Other name:
ABL001
Summary:
The Drugs Controller General of India (DCGI) has granted approval for Asciminib
film-coated 40 mg tablets on 20 Oct 2023 with the condition to perform a Phase IV
clinical study in Indian patients with Philadelphia chromosome-positive chronic myeloid
leukemia in chronic phase (Ph+ CML-CP) per the India Prescribing Information (PI). The
purpose of this prospective, multicenter, single-arm, open-label, Phase IV study is,
therefore, to confirm the safety and efficacy of Asciminib in Indian patients with Ph+
CML-CP (without threonine-315 residue with isoleucine [T315I] mutation), previously
treated with 2 or more tyrosine kinase inhibitors (TKIs) and patients with Ph+ CML-CP
with T315I mutation.
Detailed description:
This is a Phase IV, prospective, multicenter, single-arm, open-label, post-authorization
interventional study to assess the safety and efficacy of asciminib in Indian
participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more
TKIs and participants with Ph+ CML-CP with T315I mutation irrespective of the line of
treatment.
The study will include 3 periods: a screening period (up to 21 days), a treatment period
of up to 6 months with asciminib (with dosing according to mutation status), and a safety
follow-up period for 30 days after the last dose of the study treatment. Completion of
the safety follow-up period after the last dose of the study treatment will be considered
as the End of Study (EOS).
After obtaining the written informed consent form (ICF) from the participant or their
legally authorized representatives (LARs), the participants will undergo screening
procedures to confirm their eligibility for the study.
The results of the breakpoint cluster region gene-Abelson proto-oncogene 1, nonreceptor
tyrosine kinase gene (BCR::ABL1) real-time quantitative polymerase chain reaction
(RQ-PCR) as well as the T315I mutation report need to be established and documented prior
to enrollment into the study in the screening period in line with the inclusion criteria
of the study. Participants with previously documented T315I mutated CML-CP will be
directly considered for the screening procedures. If the status of the T315I mutation is
not known, the participant will undergo a standardized Sanger
sequencing/PCR/next-generation sequencing (NGS)-based T315I mutation test (as per the
availability at the site).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study.
- Male or female participants ≥18 years of age at the screening visit with a confirmed
diagnosis of Ph+ CML-CP.
Participants must meet all of the following laboratory values as confirmed by the
available reports of the peripheral blood test or bone marrow examination (performed
within 12 months before the screening) at the screening visit to meet the criteria of Ph+
CML-CP:
- <15% blasts in peripheral blood and/or bone marrow
- <30% blasts plus promyelocytes in peripheral blood and/or bone marrow
- <20% basophils in the peripheral blood
- ≥50 x 109/L (≥50,000/mm3) platelets#
- No evidence of extramedullary leukemic involvement, apart from hepatosplenomegaly.
#Transient prior therapy related thrombocytopenia (<50,000/mm3 for ≤30 days prior to
screening) is acceptable.
- a. For Ph+ CML-CP participants with T315I mutation, mutational analysis testing
at any time point showing a documented T315I mutation.
b. For Ph+ CML-CP participants without T315I mutation, at least 2 prior ATP-site
TKIs (i.e., imatinib, nilotinib, bosutinib, dasatinib, or ponatinib) with failure*
(adapted from the 2020 European LeukemiaNet [ELN] Recommendations) or intolerance**
to the most recent TKI therapy at the time of screening.
*Failure for Ph+ CML-CP participants (CP at the time of initiation of last therapy)
is defined as meeting at least one of the following criteria:
- Three months after the initiation of therapy: >10% BCR::ABL1 on IS if confirmed
within 1-3 months
- Six months after the initiation of therapy: BCR::ABL1 ratio >10% IS
- Twelve months after initiation of therapy: BCR::ABL1 ratio >1% IS
- At any time after the initiation of therapy, loss of CHR, MR2
- At any time after the initiation of therapy, the development of new BCR::ABL1
mutations which potentially cause resistance to current treatment
- At any time 12 months after the initiation of therapy, BCR::ABL1 ratio ≥1% IS or
loss of MMR
- At any time after the initiation of therapy, new clonal chromosome abnormalities in
Ph+ cells (CCA/Ph+)
**Intolerance is defined as:
- Non-hematologic toxicity: Participants with grade .3 or 4 toxicity while on therapy,
or with persistent grade 2 toxicity, unresponsive to optimal management,including
dose adjustments (unless dose reduction is not considered in the best interest of
the participant if the response is already suboptimal)
- Hematologic toxicity: Participants with grade 3 or 4 toxicity (absolute neutrophil
count [ANC] or platelets) while on therapy that is recurrent after dose reduction to
the lowest doses recommended by India PI.
- ECOG performance status of 0, 1, or 2.
- Evidence of typical BCR::ABL1 transcript (e14a2 and/or e13a2) at the time of
screening which is amenable to standardized RQ-PCR quantification.
- Participants must have adequate end organ function as per the investigator's
judgement.
- Participants must have the following electrolyte values within normal limits or
corrected to be within normal limits with supplements prior to the first dose
of study treatment:
- Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if
associated with creatinine clearance within normal limits)
- Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dL
or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance
within normal limits)
- Magnesium, except for magnesium increase >upper level of normal (ULN) - 3.0 mg/dL or
>ULN - 1.23 mmol/L associated with creatinine clearance (calculated using
Cockcroft-Gault formula) within normal limits.
Exclusion Criteria:
- Known second chronic phase of CML after previous progression to CML-AP/CML-BC.
- Previous treatment with a hematopoietic stem-cell transplantation.
- Cardiac or cardiac repolarization abnormality, including any of the following:
- History within 6 months prior to starting study treatment of myocardial
infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),
complete left bundle branch block, high-grade atrioventricular (AV) block
(e.g., bifascicular block, Mobitz type II and third-degree AV block)
- QT corrected for heart rate by Fridericia's cube root formula (QTcF) at
screening ≥450 msec (both male and female participants)
- Long QT syndrome, family history of idiopathic sudden death or congenital long
QT syndrome, or any of the following:
- Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia.
- Inability to determine the QTcF interval.1. Known second chronic phase of CML after
previous progression to CML-AP/CML-BC.
- Previous treatment with a hematopoietic stem-cell transplantation.
- Cardiac or cardiac repolarization abnormality, including any of the following:
- History within 6 months prior to starting study treatment of myocardial
infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),
complete left bundle branch block, high-grade atrioventricular (AV) block
(e.g., bifascicular block, Mobitz type II and third-degree AV block)
- QT corrected for heart rate by Fridericia's cube root formula (QTcF) at
screening ≥450 msec (both male and female participants)
- Long QT syndrome, family history of idiopathic sudden death or congenital long
QT syndrome, or any of the following:
- Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia.
- Inability to determine the QTcF interval
- Concomitant medication(s) with a "Known risk of TdP" (per www.crediblemeds.org) that
cannot be discontinued or replaced 7 days prior to starting study treatment by safe
alternative medication.
- 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 (e.g., uncontrolled diabetes, active or uncontrolled infection, pulmonary
hypertension).
- History of acute pancreatitis within 1 year of study entry or past medical history
of chronic pancreatitis.
- Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
- Known presence of significant congenital or acquired bleeding disorder unrelated to
cancer.
- History of other active malignancy within 3 years prior to study entry with the
exception of previous or concomitant basal cell skin cancer and previous carcinoma
in situ treated curatively.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass
surgery).
- Previous treatment with or known/suspected hypersensitivity to asciminib or any of
its excipients.
- Participants must avoid consumption of grapefruit, Seville oranges, or products
containing the juice of each during the entire study and 7 days before the first
dose of study treatment, due to potential CYP3A4 interaction with the study
treatment. Orange juice is allowed. Participants must avoid consumption of
over-the-counter medications or herbal supplements as these can interact with each
other and may alter the effects of asciminib.
- Participation in a prior investigational study within 30 days prior to enrollment or
within 5 half-lives of the investigational product, whichever is longer.
- Pregnant or breastfeeding women.
- Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant unless they are using highly effective methods of contraception.
Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the
participant). Note that periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
- Female sterilization (have had surgical bilateral oophorectomy (with or without
hysterectomy) total hysterectomy or bilateral tubal ligation at least 6 weeks before
taking study treatment). In the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone level
assessment.
- Male sterilization (vasectomy) of the male partner(s) of the female participant at
least 6 months prior to screening. The vasectomized male partner should be the sole
partner for that participant.
- Use of oral, injected, or implanted hormonal methods of contraception or placement
of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
hormonal contraception that have comparable efficacy (failure rate <1%), for
example, hormone vaginal ring or transdermal hormone contraception. In the case of
the use of oral contraception, women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
- Women are considered post-menopausal and not of childbearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g., age-appropriate history of vasomotor symptoms) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least 6 weeks before taking
study treatment. In the case of oophorectomy alone, women are considered menopausal
and not of childbearing potential only when the reproductive status of the woman has
been confirmed by a follow-up hormone level assessment.
- If a participant is presenting with symptoms suggestive of possible Coronavirus
Disease (COVID-19) infection, advise ruling it out by appropriate testing
recommended by health authorities.
- Nucleic acid amplification tests for viral RNA (polymerase chain reaction), to
measure current infection with SARS-CoV-2
- Antigen tests for rapid detection of SARS-CoV-2
- Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
October 15, 2024
Completion date:
April 23, 2025
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06427811
