CTRI/2024/10/075881 [Registered on: 25/10/2024] Trial Registered Prospectively
Last Modified On:
10/09/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Clinical Study of Asciminib in Previously Treated Indian Patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase.
Scientific Title of Study
A Prospective, Multicenter, Single-arm, Open-label, Phase IV, Post-authorization Interventional Study to Assess the Safety and Efficacy of Asciminib in Indian Patients with Ph positive CML-CP (Without T315I Mutation) Previously Treated with two or more Tyrosine Kinase Inhibitors and Ph Positive CML-CP with T315I Mutation.
All India Institute of Medical
Sciences, Room No:218, 2nd floor Dr. B. R. A. Institute Rotary Cancer Hospital,
Ansari Nagar, New Delhi, 110029
New Delhi DELHI
9013956187
drranjitmd@gmail.com
Dr Velu Nair
Apollo Hospital International Limited, Apollo cancer centre
Apollo Hospital Internation Limited, Apollo cancer center
Plot1A,Bhat,GIDC,Gandhinagar,
Gujrat,382428
Gandhinagar GUJARAT
9920273063
nairvelu2000@yahoo.com
Dr Jina Bhattacharyya
Gauhati Medical College and Hospital
Department of Clinical Hematology,3rd floor, project office
Kamrup ASSAM
9435557491
drjinabhattacharyya@yahoo.co.in
Dr Sanket Shah Prashantbhai
Hemato Oncology Clinic Ahmedabad PVT LTD- HOC Vedanta
Hemato Oncology, Ground floor & first floor, room no 210 Ahmadabad GUJARAT
9909908620
drsanket2086@gmail.com
Dr Sadashivudu G
Nizam’s Institute of Medical Sciences, Hyderabad
Department of Medical Oncology, Nizam Institute of Medical Sciences, Punjagutta, Hyderabad -500082, Telangana, India Hyderabad TELANGANA
9440911865
drssgundeti@yahoo.com
Dr Tuphan Kanti Dolai
NRS Medical College and Hospital
Hematology Department, room no-1 Kolkata WEST BENGAL
9874890275
tkdolai75@gmail.com
Dr Sugeeth M T
Regional Cancer Centre
Medical Oncology Department
Room number : B5 (01),Sixth floor,B block, Old Building Regional Cancer Centre , Medical College Campus, Medical College P.O Thiruvananthapuram- 695011
Thiruvananthapuram KERALA
9496324153
sugeethmt@ymail.com
Dr Shashikant Apte
Sahyadri Super Speciality Hospital
Sahyadri Super Speciality Hospital Nagar Road
Survey No. 185 A, Shastri Nagar,
Near MSEB Office Yerwada,
Nagar Road, Pune-411006, Maharashtra, India
Pune MAHARASHTRA
9822404983
shashikant.apte@gmail.com
Dr Sudha Sethy
SCB Medical College & Hospital
SCB Medical College & Hospital
Department of Clinical Hematology, Room no-1,
1st Floor, Old Medicine Building,
Cuttack – 753007
Cuttack ORISSA
9337016545
drsudhasethy@gmail.com
Dr Seetharam Anandram
St Johns Medical College Hospital
St Johns Medical College Hospital,
Department of Clinical Hematology, Sarjapur Road, Bangalore- 560034
Bangalore KARNATAKA
80 mg BID or 200mg BID orally daily, for 6 months.
Comparator Agent
NIL
NIL
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Confirmed diagnosis of Ph+ CML-CP.
2. 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:
a) More than 15% blasts in peripheral blood and/or bone marrow
b) More than 30% blasts plus promyelocytes in peripheral blood and/or bone marrow
c) More than 20% basophils in the peripheral blood
d) More than and equal to 50 x 109/L (≥50,000/mm3) platelets
e) No evidence of extramedullary leukemic involvement, apart from hepatosplenomegaly
3. For Ph+ CML-CP participants with T315I mutation, mutational analysis testing at any time point showing a documented T315I mutation.
For Ph+ CML-CP participants without T315I mutation, at least 2 prior adenosine triphosphate (ATP)-site TKIs (i.e., imatinib, nilotinib, bosutinib, dasatinib, or ponatinib) with failure (adapted from the 2020 European Leukemia Net [ELN] Recommendations) or intolerance to the most recent TKI therapy at the time of screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5. Evidence of typical BCR/ABL1 transcript (e14a2 and or e13a2) at the time of screening which is amenable to standardized RQ-PCR quantification.
6. Participants must have adequate end organ function as per the investigator’s judgement.
7. 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:
a. Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits).
b. 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).
c. Magnesium, except for magnesium increase more than upper level of normal (ULN) – 3.0 mg/dL or more than ULN – 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits.
ExclusionCriteria
Details
1. Known second chronic phase of CML after previous progression to CML-acute phase (AP)/CML-blast crisis (BC).
2. Previous treatment with a hematopoietic stem-cell transplantation.
3. Cardiac or cardiac repolarization abnormality, including any of the following:
a. History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG)
b. 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)
c. QT corrected for heart rate by Fridericia’s cube root formula (QTcF) at screening ≥450 msec (both male and female participants)
d. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
i) Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
ii) Inability to determine the QTcF interval.
4. 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.
5. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
6. Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
7. Known presence of significant congenital or acquired bleeding disorder unrelated to cancer.
8. Previous treatment with or known/suspected hypersensitivity to asciminib or any of its excipients.
9. 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.
10. Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
11. Pregnant or breastfeeding women.
12. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception.
13. 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.
14. Nucleic acid amplification tests for viral RNA (polymerase chain reaction), to measure current infection with SARS-CoV-2
15. Antigen tests for rapid detection of SARS-CoV-2
16. Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
1. Frequency and severity of adverse events (AEs)/serious AEs (SAEs) in participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs up to 6 months
2. Frequency and severity of AEs/SAEs in participants with Ph+ CML-CP with T315I mutation
upto 6 months
Secondary Outcome
Outcome
TimePoints
Ph+ CML-CP Previously treated with 2 or more TKI’s (without T3151 mutation)
1. Proportion of participants with dose interruptions, reductions, & discontinuation up to 6 months
2. Percentage of participants achieving a complete hematologic response (CHR) at 3 & 6 months of the treatment period
3. Percentage of participants achieving early molecular response (EMR), molecular response (MR2), major molecular response (MMR), & molecular response of MR4 & MR4.5 at 3 & 6 months of the treatment period
4. Time to achieve CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment period
During 6 months of the treatment period
Ph+ CML-CP with T3151 mutation
1. Proportion of participants with dose interruptions, reductions, & discontinuation up to 6 months
2. Percentage of participants achieving a CHR at 3 & 6 months of the treatment period
3. Percentage of participants achieving EMR, MR2, MMR, MR4, & MR4.5 at 3 & 6 months of the treatment period
4. Time to achieve CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment period
5. Duration of CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment period
During the 6 months treatment period
Target Sample Size
Total Sample Size="85" Sample Size from India="85" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is 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 T3151 mutation) previously treated with 2 or more TKIs and
participants with Ph+ CML-CP with T3151 mutation irrespective of the line of
treatment
The study will include 3 periods, a screening
period (upto 21 Days), a treatment period of upto 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 end of
study (EOS).