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Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

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ClinicalTrials.gov Identifier: NCT03578367
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 15, 2018
First Posted Date  ICMJE July 6, 2018
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE November 22, 2018
Estimated Primary Completion Date November 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone [ Time Frame: at 48 weeks ]
Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 (Fusion gene from breakpoint cluster region and Abelson genes) ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and imatinib alone
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03578367 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
  • MR^4.5 rate at 48 weeks [ Time Frame: at 48 weeks ]
    Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
  • Rate of MR^4.5 at 96 weeks [ Time Frame: at 96 weeks ]
    Proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks
  • Rate of MR^4.5 by 48 and 96 weeks [ Time Frame: by 48 weeks and 96 weeks ]
    Best observed rate of MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point
  • Sustained MR^4.5 from 48 weeks until 96 weeks [ Time Frame: from 48 weeks until 96 weeks ]
    Percentage of participants who are in MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at both 48 and 96 weeks and who have no loss of MR^4.5 in between those two time points. This endpoint will be analyzed at 96 weeks.
  • Time to MR^4.5 [ Time Frame: up to 96 weeks ]
    Time to MR^4.5 is the time from randomization to first MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR^4.5
  • Difference in rate of MR^4.5 at 48 weeks [ Time Frame: at 48 weeks ]
    Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
  • Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax [ Time Frame: up to Week 4 Day 28 ]
    The maximum (peak) observed drug concentration after dose administration
  • Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax [ Time Frame: up to Week 4 Day 28 ]
    The time to reach maximum (peak) drug concentration after dose administration
  • Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin [ Time Frame: up to 96 weeks ]
    Minimum drug concentration
  • Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast [ Time Frame: up to Week 4 Day 28 ]
    The AUC from time zero to the last measurable concentration sampling time (Tlast)
  • Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau [ Time Frame: up to Week 4 Day 28 ]
    The AUC calculated to the end of a dosing interval (tau) at steady-state
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)
Official Title  ICMJE A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response
Brief Summary To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CML
  • Chronic Myelogenous Leukemia
  • Leukemia, Myeloid Chronic
  • Hematologic Diseases
Intervention  ICMJE
  • Drug: Asciminib add-on
    Asciminib 60 mg or 40 mg taken orally once daily in addition to Imatinib 400 mg taken orally once daily
    Other Name: ABL001 (asciminib), STI571 (imatinib)
  • Drug: Imatinib
    Imatinib 400 mg taken orally once daily
    Other Name: STI571, continuation treatment
  • Drug: Nilotinib
    Nilotinib 300 mg taken orally twice daily (total daily dose of 600 mg)
    Other Name: AMN107, switch to nilotinib treatment
Study Arms  ICMJE
  • Experimental: Asciminib 60mg QD + Imatinib 400mg QD
    Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily
    Intervention: Drug: Asciminib add-on
  • Experimental: Asciminib 40mg QD + Imatinib 400mg QD
    Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily
    Intervention: Drug: Asciminib add-on
  • Active Comparator: Imatinib 400mg QD
    Imatinib 400 mg taken once daily
    Intervention: Drug: Imatinib
  • Active Comparator: Nilotinib 300mg BID
    Nilotinib 300 mg taken twice daily
    Intervention: Drug: Nilotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 20, 2021
Estimated Primary Completion Date November 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients ≥ 18 years of age with a confirmed diagnosis of Chronic Myeloid Leukemia in chronic phase (CML-CP).
  2. Minimum of two years (24 calendar months) treatment with imatinib first line for CML-CP (patients have to be on imatinib 400 mg QD at randomization and had no dose change in the past three months).
  3. BCR-ABL1 levels > 0.01% IS (International Scale) and ≤ 1% IS at the time of study entry as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (MR4 IS) at any time during prior imatinib treatment.
  4. Patient must meet the following laboratory values before randomization:

    • Absolute Neutrophil Count ≥ 1.5 x 10E9/L
    • Platelets ≥ 75 x 10E9/L
    • Hemoglobin ≥ 9 g/dL
    • Serum creatinine < 1.5 mg/dL
    • Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal) except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN
    • Aspartate transaminase (AST) ≤ 3.0 x ULN
    • Alanine transaminase (ALT) ≤ 3.0 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN
  5. Patients must have the following laboratory values ≥ Lower Limit of Normal or corrected to within normal limits with supplements prior to randomization: potassium, magnesium, phosphorus, total calcium (corrected for serum albumin).

Key Exclusion Criteria:

  1. Treatment failure according to European Leukemia Network (ELN) criteria 2013 during imatinib treatment.
  2. Known second chronic phase of CML after previous progression to Accelerated Phase (AP)/Blast Crisis (BC).
  3. Previous treatment with any tyrosine kinese inhibitors (TKIs) other than imatinib.
  4. History or current diagnosis of ECG abnormalities indicating significant risk or safety for subjects participating in the study such as:

    • History of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
    • Concomitant clinically significant arrhythmias
    • Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to randomization
    • 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
      • Concomitant medications with a "known" risk of Torsades de Pointes
      • inability to determine the QTcF interval
  5. 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, uncontrolled clinically significant hyperlipidemia and high serum amylase)
  6. History of acute pancreatitis within 1 year prior to randomization or past medical history of chronic pancreatitis.
  7. History of other active malignancy within 3 years prior to randomization with the exception of basal cell skin cancer, indolent prostate cancer and carcinoma in situ treated curatively.

Other protocol defined inclusion/exclusion may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   Czechia,   Denmark,   France,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Poland,   Portugal,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03578367
Other Study ID Numbers  ICMJE CABL001E2201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP