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

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ClinicalTrials.gov Identifier: NCT02709083
Recruitment Status : Terminated (Original principal investigator left institution)
First Posted : March 15, 2016
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
William Blum, Emory University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia Chronic Myeloid Leukemia Leukemia Drug: Dasatinib Drug: Imatinib Mesylate Drug: Nilotinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-Line Dasatinib or Nilotinib Followed by Response Guided Switch to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
Study Start Date : October 2016
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018


Arm Intervention/treatment
Experimental: Treatment-dasatinib, nilotinib, imatinib
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.
Drug: Dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel

Drug: Imatinib Mesylate
Given orally
Other Names:
  • CGP57148B
  • Gleevec
  • Glivec
  • STI-571

Drug: Nilotinib
Given orally
Other Names:
  • AMN 107
  • Tasigna




Primary Outcome Measures :
  1. The Proportion of Subjects Who Achieve Major Molecular Response (MMR) [ Time Frame: At 12 months ]
    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 :
  1. 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 ]
    Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP).

  2. 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 ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    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.

  7. 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT02709083


Locations
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United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: William Blum, MD Emory University
  Study Documents (Full-Text)

Documents provided by William Blum, Emory University:
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Responsible Party: William Blum, Acting Professor, Emory University
ClinicalTrials.gov Identifier: NCT02709083    
Other Study ID Numbers: IRB00087045
NCI-2016-00162 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship3143-16 ( Other Identifier: Emory University/Winship Cancer Institute )
First Posted: March 15, 2016    Key Record Dates
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018
Last Verified: November 2018
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action