Clinical Trials /

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

NCT03578367

Description:

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)

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CABL001E2201
  • NCT ID: NCT03578367

Conditions

  • CML
  • Chronic Myelogenous Leukemia
  • Leukemia, Myeloid Chronic
  • Hematologic Diseases

Interventions

DrugSynonymsArms
Asciminib add-onABL001 (asciminib), STI571 (imatinib)Asciminib 60mg QD + Imatinib 400mg QD
ImatinibSTI571, continuation treatmentImatinib 400mg QD
NilotinibAMN107, switch to nilotinib treatmentNilotinib 300mg BID

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
Asciminib 60mg QD + Imatinib 400mg QDExperimentalAsciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily
  • Asciminib add-on
Asciminib 40mg QD + Imatinib 400mg QDExperimentalAsciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily
  • Asciminib add-on
Imatinib 400mg QDActive ComparatorImatinib 400 mg taken once daily
  • Imatinib
Nilotinib 300mg BIDActive ComparatorNilotinib 300 mg taken twice daily
  • Nilotinib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone
Time Frame:at 48 weeks
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:MR^4.5 rate at 48 weeks
Time Frame:at 48 weeks
Safety Issue:
Description:Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Measure:Rate of MR^4.5 at 96 weeks
Time Frame:at 96 weeks
Safety Issue:
Description:Proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks
Measure:Rate of MR^4.5 by 48 and 96 weeks
Time Frame:by 48 weeks and 96 weeks
Safety Issue:
Description:Best observed rate of MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point
Measure:Sustained MR^4.5 from 48 weeks until 96 weeks
Time Frame:from 48 weeks until 96 weeks
Safety Issue:
Description: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.
Measure:Time to MR^4.5
Time Frame:up to 96 weeks
Safety Issue:
Description: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
Measure:Difference in rate of MR^4.5 at 48 weeks
Time Frame:at 48 weeks
Safety Issue:
Description:Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Measure:Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax
Time Frame:up to Week 4 Day 28
Safety Issue:
Description:The maximum (peak) observed drug concentration after dose administration
Measure:Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax
Time Frame:up to Week 4 Day 28
Safety Issue:
Description:The time to reach maximum (peak) drug concentration after dose administration
Measure:Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin
Time Frame:up to 96 weeks
Safety Issue:
Description:Minimum drug concentration
Measure:Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast
Time Frame:up to Week 4 Day 28
Safety Issue:
Description:The AUC from time zero to the last measurable concentration sampling time (Tlast)
Measure:Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau
Time Frame:up to Week 4 Day 28
Safety Issue:
Description:The AUC calculated to the end of a dosing interval (tau) at steady-state

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • CML
  • Chronic Myelogenous Leukemia
  • leukemia, myeloid chronic
  • Hematologic Diseases
  • Asciminib
  • ABL001
  • Imatinib
  • Nilotinib
  • deep molecular response
  • DMR
  • Ph+ CML
  • chronic phase
  • cancer of the white blood cells
  • tyrosine kinase inhibitor
  • leukemia, myeloid
  • leukemia

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