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

• Sponsor: Emory University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02709083
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 21
• Patients Per Site Per Month: 0.3

Study Details

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:

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

SECONDARY OBJECTIVES:

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

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

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

4. To assess safety.

5. To assess patient reported outcomes (PRO).

TERTIARY OBJECTIVES:

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

2. 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
• 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: Oct 1, 2016
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 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) [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 [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) [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 [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 [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) [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 [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) [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

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Jun 21, 2017

More Information

Publications

None provided.

• Responsible Party: William Blum, Acting Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02709083
• Other Study ID Numbers: IRB00087045; NCI-2016-00162; Winship3143-16
• First Posted: Mar 15, 2016
• Last Update Posted: Nov 2, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Imatinib Mesylate; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Period Title: Overall Study
STARTED	7
COMPLETED	0
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Overall Participants	7
Age, Customized (Count of Participants)
Age 20-29	2 28.6%
Age 30-39	3 42.9%
Age 40-49	0 0%
Age 50-59	0 0%
Age 60-69	1 14.3%
Age 70-79	1 14.3%
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	7 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 14.3%
White	4 57.1%
More than one race	0 0%
Unknown or Not Reported	2 28.6%
Region of Enrollment (Count of Participants)
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects Who Achieve Major Molecular Response (MMR)
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%).
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

2. Secondary Outcome

Title	Accelerated Phase (AP) or Blast Phase (BP) Free Survival
Description	Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP).
Time Frame	The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

3. Secondary Outcome

Title	Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML)
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.
Time Frame	Baseline to up to 12 months

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

4. Secondary Outcome

Title	Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
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.
Time Frame	Up to 30 days after the end-of-treatment

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

5. Secondary Outcome

Title	Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria
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.
Time Frame	Up to 30 days after the end-of-treatment

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

6. Secondary Outcome

Title	Progression Free Survival (PFS)
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.
Time Frame	The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

7. Secondary Outcome

Title	Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria
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.
Time Frame	Up to 30 days after the end-of-treatment

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

8. Secondary Outcome

Title	The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴)
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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.

Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
Measure Participants	0

Adverse Events

Time Frame	Adverse events were recorded, concluding 30 days following the last dose of the assigned study treatment.
Arm/Group Title	Treatment-dasatinib, Nilotinib, Imatinib
Arm/Group Description	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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally
All Cause Mortality
	Treatment-dasatinib, Nilotinib, Imatinib
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Treatment-dasatinib, Nilotinib, Imatinib
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Treatment-dasatinib, Nilotinib, Imatinib
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

Trial was terminated early due to original study principal investigator Vamsi Kota, MD, leaving Emory University.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.