Chronic Myelogenous Leukemia, Chronic Myeloid Leukemia, Leukemia
Conditions
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.
Interventions
DRUGDasatinib
Given orally
DRUGImatinib Mesylate
Given orally
DRUGNilotinib
Given orally
Sponsors
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Original PI left institution | 7 |
Baseline characteristics
| Characteristic | Treatment-dasatinib, Nilotinib, Imatinib |
|---|---|
| Age, Customized Age 20-29 | 2 Participants |
| Age, Customized Age 30-39 | 3 Participants |
| Age, Customized Age 40-49 | 0 Participants |
| Age, Customized Age 50-59 | 0 Participants |
| Age, Customized Age 60-69 | 1 Participants |
| Age, Customized Age 70-79 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
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%).
Time frame: At 12 months
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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).
Time frame: The time of CML diagnosis to the time of transformation to AP or BP, assessed up to 24 months
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: Baseline to up to 12 months
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: Up to 30 days after the end-of-treatment
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: Up to 30 days after the end-of-treatment
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: The time of CML diagnosis to the time of loss of MMR or loss of hematologic response, assessed up to 24 months
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: Up to 30 days after the end-of-treatment
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.
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.
Time frame: Up to 24 months
Population: Data not collected since trial closed early; original study principal investigator Vamsi Kota, MD, left Emory University.