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

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

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, Georgia

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: William Blum, MD; Emory University

  Study Documents (Full-Text)

Documents provided by William Blum, Emory University:

Study Protocol and Statistical Analysis Plan  [PDF] June 21, 2017

More Information

• 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
• Results First Posted: November 2, 2018
• Last Update Posted: November 2, 2018
• Last Verified: November 2018

Additional relevant MeSH terms:

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