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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-00162 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| Winship3143-16 | Other Identifier | Emory University/Winship Cancer Institute |
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Original principal investigator left institution
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment-dasatinib, nilotinib, imatinib | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dasatinib | Drug | Given orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Proportion of Subjects Who Achieve Major Molecular Response (MMR) | 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%). | At 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Accelerated Phase (AP) or Blast Phase (BP) Free Survival | Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP). | The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months |
| Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William Blum, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University/Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 21, 2017 |
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| Imatinib Mesylate | Drug | Given orally |
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| Nilotinib | Drug | Given orally |
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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. |
| Baseline to up to 12 months |
| Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria | 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. | Up to 30 days after the end-of-treatment |
| Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria | 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. | Up to 30 days after the end-of-treatment |
| Progression Free Survival (PFS) | 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. | The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months |
| Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria | 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. | Up to 30 days after the end-of-treatment |
| The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴) | 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. | Up to 24 months |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Proportion of Subjects Who Achieve Major Molecular Response (MMR) | 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%). | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | At 12 months |
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| Secondary | Accelerated Phase (AP) or Blast Phase (BP) Free Survival | Survival will be defined as the time from CML diagnosis to the time of transformation to accelerated phase (AP) or blast phase (BP). | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months |
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| Secondary | Change in Patient Reported Outcomes (PRO) Score Extracted From the MD Anderson Symptom Inventory-Chronic Myelogenous Leukemia (CML) | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | Baseline to up to 12 months |
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| Secondary | Duration of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | Up to 30 days after the end-of-treatment |
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| Secondary | Frequency of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Criteria | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | Up to 30 days after the end-of-treatment |
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| Secondary | Progression Free Survival (PFS) | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months |
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| Secondary | Severity of Adverse Events (AEs) Using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Criteria | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | Up to 30 days after the end-of-treatment |
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| Secondary | The Number of Subjects With Breakpoint Cluster Region-abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Transcript Levels ≤ Deep Molecular Responses (MR⁴) | 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. | Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University. | Posted | Up to 24 months |
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Adverse events were recorded, concluding 30 days following the last dose of the assigned study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Dasatinib: Given orally Imatinib Mesylate: Given orally Nilotinib: Given orally | 0 | 7 | 0 | 7 | 0 | 7 |
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Trial was terminated early due to original study principal investigator Vamsi Kota, MD, leaving Emory University.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| William Blum, MD | Emory University | 404-778-1900 | william.g.blum@emory.edu |
| Aug 14, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| D000068877 | Imatinib Mesylate |
| C498826 | nilotinib |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D001549 | Benzamides |
| D000577 | Amides |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
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| Title | Measurements |
|---|
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| Age 50-59 |
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| Age 60-69 |
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| Age 70-79 |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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