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Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

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ClinicalTrials.gov Identifier: NCT04795427
Recruitment Status : Recruiting
First Posted : March 12, 2021
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.


Condition or disease Intervention/treatment Phase
Leukemia, Chronic Myelogenous Drug: asciminib Other: best available treatment Phase 2

Detailed Description:

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio > 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors
Actual Study Start Date : December 6, 2021
Estimated Primary Completion Date : December 22, 2023
Estimated Study Completion Date : February 4, 2025


Arm Intervention/treatment
Experimental: asciminb arm
Patients will receive asciminib (40 mg BID continuous)
Drug: asciminib
Asciminib comes in 20 mg and 40 mg tablets and is taken orally twice daily
Other Name: ABL001

Experimental: best available treatment arm
Patients will receive best available therapy chosen by investigator
Other: best available treatment
Best available treatment will be based on investigator's choice identified prior to randomization. Dose and frequency will depend on label and institutional guidelines for various BAT




Primary Outcome Measures :
  1. Major molecular response rate of asciminib [ Time Frame: week 24 ]
    Evaluate the major molecular response rate at 24 weeks in asciminib arm


Secondary Outcome Measures :
  1. Cytogenetic response (CyR) rate [ Time Frame: 24, 48, 96 weeks ]
    Evaluate the cytogenetic response rate (Complete, Partial, Major, Minor, Minimal, no response) at and by all scheduled data collection time points including 24, 48 and 96 weeks for both asciminib arm and best available treatment arm.

  2. Major molecular response rate of best available treatment arm [ Time Frame: week 24 ]
    Evaluate the major molecular response rate at week 24 of best available treatment arm, and compare with asciminib arm

  3. Major molecular response rate of both asciminib arm and BAT armn time points [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment, except week 24 ]
    Evaluate the major molecular response rate, collected at all scheduled data collection time point (except week 24)

  4. major molecular response rate by all scheduled data collection time points [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment ]
    Evaluate the major molecular rate by all scheduled data collection time points including 24, 48 and 96 weeks by treatment group

  5. Time to major molecular response rate [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment ]
    Evaluate the time from the date of the first dose of study drug to the date of the first documented MMR by treatment group

  6. Duration of major molecular response [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment ]
    First document major molecular response to loss of MMR up to 96 weeks after last participant receive the first dose

  7. Overall survival [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up ]
    To evaluate the time from the date of randomization to the date of death (including the survival follow-up period)

  8. Progression free survival [ Time Frame: Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up ]
    Evaluate the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause (including progressions and deaths observed during the survival follow-up period)

  9. Pharmacokinetics (PK) parameter of asciminib: Cmax [ Time Frame: week 2 day 1, week 4, week 12, week 24 and week 96 ]
    Characterize PK of asciminib in the Chinese CML-CP population. Cmax is the maximum (peak) observed plasma drug concentration after dose administration (ng/mL).

  10. PK parameter of asciminib: Tmax [ Time Frame: week 2 day 1, week 4, week 12, week 24 and week 96 ]
    Characterize PK of asciminib in the Chinese CML-CP population. Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).

  11. PK parameter of asciminib: Ctrough [ Time Frame: week 2 day 1, week 4, week 12, week 24 and week 96 ]
    Characterize PK of asciminib in the Chinese CML-CP population. Trough plasma concentrations (Ctrough)

  12. PK parameter of asciminib: AUCtau [ Time Frame: week 2 day 1, week 4, week 12, week 24 and week 96 ]
    Characterize PK of asciminib in the Chinese CML-CP population. The partial area under the plasma concentration-time curve from dose time to tau (ng*hr/mL). For a bid regimen, Tau=12h.

  13. PK parameter of asciminib: AUClast [ Time Frame: week 2 day 1, week 4, week 12, week 24 and week 96 ]
    Characterize PK of asciminib in the Chinese CML-CP population. AUClast is the The AUC from the time of dosing to the time of the last measurable plasma concentration (Tlast) (ng*hr/mL)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Diagnosed as CML-CP:

  1. Participants must meet all of the following laboratory values at the screening visit:

    < 15% blasts in peripheral blood and bone marrow < 30% blasts plus promyelocytes in peripheral blood and bone marrow < 20% basophils in the peripheral blood

    • 50 x 10^9/ L (≥ 50,000/mm3) platelets Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
  2. Prior treatment with a minimum of 2 prior ATP-competitive TKIs.
  3. Failure (adapted from the 2013 European Leukemia Net (ELN) Guidelines) or intolerance to the most recent TKI therapy at the time of screening.
  4. 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:

  1. Known presence of the T315I mutation at any time prior to study entry
  2. Known second chronic phase of CML after previous progression to AP/BC
  3. Previous treatment with a hematopoietic stem cell transplantation
  4. Participants planning to undergo allogeneic hematopoietic stem cell transplantation
  5. Cardiac or cardiac repolarization abnormality, including any of the following:

    History within 6 months prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft Clinically significant cardiac arrhythmias , complete left bundle branch block, high-grade AV block QTcF at screening ≥450 msec (male participants), ≥460 msec (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 including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia Concomitant medication(s) with a "Known risk of Torsades de Pointes" that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.

    Inability to determine the QTcF interval

  6. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04795427


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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China, Guangdong
Novartis Investigative Site Recruiting
Guangzhou, Guangdong, China, 510515
China, Hubei
Novartis Investigative Site Recruiting
Wuhan, Hubei, China, 430022
China, Sichuan
Novartis Investigative Site Recruiting
Chengdu, Sichuan, China, 610041
China, Tianjin
Novartis Investigative Site Recruiting
Tianjin, Tianjin, China, 300020
China
Novartis Investigative Site Recruiting
Beijing, China, 100044
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04795427    
Other Study ID Numbers: CABL001A2202
First Posted: March 12, 2021    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Chronic Myelogenous Leukemia in chronic phase
Chronic Myelogenous Leukemia
CML-CP
Chronic
Chronic Phase
ABL001
asciminib
prior treatment with 2 or more tyrosine kinase inhibitors (TKIs)
major molecular response
MMR
Chinese patients
phase ll
open label
best available therapy
BAT
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases