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

Phase 2

Terminated

• Conditions: Leukemia; Chronic Myeloid Leukemia; Chronic Myelogenous Leukemia
• Interventions: Drug: Dasatinib; Drug: Imatinib Mesylate; Drug: Nilotinib

• Registration Number: NCT02709083
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2016-03-10
• Study First Submitted QC: 2016-03-10
• Study First Posted: 2016-03-15
• Study Start: 2016-10
• Primary Completion: 2018-07
• Study Completion: 2018-07
• Results First Submitted: 2018-08-23
• Status Verified: 2018-11
• Results First Submitted QC: 2018-11-01
• Last Update Submitted: 2018-11-01
• Results First Posted: 2018-11-02
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment-dasatinib, nilotinib, imatinib	Nilotinib	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.
Treatment-dasatinib, nilotinib, imatinib	Dasatinib	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.
Treatment-dasatinib, nilotinib, imatinib	Imatinib Mesylate	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.

Primary Outcome Measures

Name	Time	Method
The Proportion of Subjects Who Achieve Major Molecular Response (MMR)	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

Name	Time	Method
Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML)	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.
Accelerated Phase (AP) or Blast Phase (BP) Free Survival	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).
Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria	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.
Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria	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.
The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)	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.
Progression Free Survival (PFS)	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.
Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria	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.

Trial Locations

Locations (1)

Emory University/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States