Clinical Trials /

Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia

NCT02709083

Description:

This phase II trial studies how well dasatinib, nilotinib, and imatinib mesylate works in treating patients with newly diagnosed, previously untreated chronic myeloid leukemia in which fewer than 10% of the cells in the blood and bone marrow are blast cells (immature blood cells) (chronic phase). Dasatinib, nilotinib, and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02709083

Trial Eligibility

Document

Title

  • Brief Title: Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia
  • Official Title: First-Line Dasatinib or Nilotinib Followed by Response Guided Switch to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: IRB00087045
  • SECONDARY ID: NCI-2016-00162
  • SECONDARY ID: Winship3143-16
  • NCT ID: NCT02709083

Conditions

  • Chronic Myelogenous Leukemia
  • Chronic Myeloid Leukemia
  • Leukemia

Interventions

DrugSynonymsArms
DasatinibBMS-354825, SprycelTreatment-dasatinib, nilotinib, imatinib
Imatinib MesylateCGP57148B, Gleevec, Glivec, STI-571Treatment-dasatinib, nilotinib, imatinib
NilotinibAMN 107, TasignaTreatment-dasatinib, nilotinib, imatinib

Purpose

This phase II trial studies how well dasatinib, nilotinib, and imatinib mesylate works in treating patients with newly diagnosed, previously untreated chronic myeloid leukemia in which fewer than 10% of the cells in the blood and bone marrow are blast cells (immature blood cells) (chronic phase). Dasatinib, nilotinib, and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess incidence of major molecular response (MMR) at 12 months.

      SECONDARY OBJECTIVES:

      I. To assess progression free survival (PFS) at 12 and 24 months.

      II. To assess accelerated phase (AP) or blast phase (BP) transformation-free survival at 12
      and 24 months.

      III. To assess incidence of deep MRs (≥ MR⁴) at 12 months and 24 months.

      IV. To assess safety.

      V. To assess patient reported outcomes (PRO).

      TERTIARY OBJECTIVES:

      I. To assess prognostic significance of detecting aberrant myeloid or lymphoid markers on
      diagnostic bone marrow.

      II. To assess ability to enroll subjects who maintain deep molecular remissions in tyrosine
      kinase inhibitors (TKIs) discontinuation trials.

      OUTLINE:

      Patients receive dasatinib orally (PO) once a day (QD) or nilotinib PO twice a day (BID) at
      the discretion of the treating hematologist. Patients achieving either a 1 log reduction at 3
      months or a 2 log reduction at 6 months in their breakpoint cluster region-abelson murine
      leukemia viral oncogene homolog 1 (BCR-ABL1) transcript levels may switch to imatinib
      mesylate PO QD.

      After completion of study treatment, patients are followed up at 2 weeks and then up to 60
      months.

Trial Arms

NameTypeDescriptionInterventions
Treatment-dasatinib, nilotinib, imatinibExperimentalPatients receive dasatinib orally (PO) once a day (QD) or nilotinib PO twice a day (BID) at the discretion of the treating hematologist. Patients achieving either a 1 log reduction at 3 months or a 2 log reduction at 6 months in their breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcript levels may switch to imatinib mesylate PO QD.
  • Dasatinib
  • Imatinib Mesylate
  • Nilotinib

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed, previously untreated chronic phase chronic myeloid leukemia (CP-CML)
             (by World Health Organization [WHO] definition) (hydroxyurea permitted up to 7 days
             prior to enrollment)

          -  Clinically significant gastrointestinal disease, digestive dysfunction, or surgery
             that would compromise absorption of oral administration of medications

          -  Able to give written informed consent and comply with all study visits and procedures

        Exclusion Criteria:

          -  Chronic myeloid leukemia (CML) in AP or BP

          -  Unable to receive TKI for insurance reasons (uninsurable)

          -  Refuse or unable to perform telephone or video conferences with research coordinator

          -  Subjects who are pregnant, breast feeding or sexually active and unwilling to use
             effective birth control while on treatment with TKI

          -  Any medical or psychological condition that, in the opinion of the investigator, might
             interfere with the subject's participation in the trial, poses any additional risk for
             the subject, or confounds the assessment of the subject
Maximum Eligible Age:N/A
Minimum Eligible Age:17 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The Proportion of Subjects Who Achieve Major Molecular Response (MMR)
Time Frame:At 12 months
Safety Issue:
Description:Response will be measured by a decrease in fusion transcript or protein resulting from the 9;22 chromosomal translocation responsible for formation of the Philadelphia Chromosome (BCR-ABL1) levels on a logarithmic scale. A 1 log reduction is a drop to below 10%, while a major molecular response (MMR) is defined as a 3 log reduction (0.1%).

Secondary Outcome Measures

Measure:Accelerated Phase (AP) or Blast Phase (BP) Free Survival
Time Frame:The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months
Safety Issue:
Description:Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP).
Measure:Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML)
Time Frame:Baseline to up to 12 months
Safety Issue:
Description:The patient reported outcomes (PRO) score extracted from the MD Anderson Symptom Inventory (MDASI)-Chronic Myelogenous Leukemia (CML) will be determined and intra and inter subject changes will be compared.
Measure:Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Time Frame:Up to 30 days after the end-of-treatment
Safety Issue:
Description:Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measure:Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria
Time Frame:Up to 30 days after the end-of-treatment
Safety Issue:
Description:Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measure:Progression Free Survival (PFS)
Time Frame:The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months
Safety Issue:
Description:Progression free survival (PFS) will be defined as the time from CML diagnosis to the time of loss of major molecular response (MMR) or loss of hematologic response.
Measure:Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
Time Frame:Up to 30 days after the end-of-treatment
Safety Issue:
Description:Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented. Exposure to drug over time will also be summarized. The AE incidence rates, as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described as obtained from subject forms and subject communications.
Measure:The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)
Time Frame:Up to 24 months
Safety Issue:
Description:Descriptive statistics will summarize the changes in breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) testing over time will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Emory University

Last Updated

November 2, 2018