Leukemia, Myeloid, Chronic
Conditions
Brief summary
This is a non-randomized, prospective, single-group longitudinal study. The purpose of this study is to improve the decision making process used by physicians and patients when they are considering stopping their Tyrosine Kinase Inhibitor (TKI) medication.
Detailed description
This is a non-randomized, prospective, single-group longitudinal study. The overall objective is to improve decision making for TKI discontinuation in eligible chronic myelogenous leukemia (CML) patients. Patients with CML on treatment with imatinib, dasatinib, nilotinib, or bosutinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years. The study will closely monitor patients using standard real-time Quantitative Polymerase Chain Reaction (RQ-PCR) testing for molecular recurrence, testing them monthly for six months, then every other month until 24 months, and then quarterly until 36 months. Concurrently, the study will assess a wide range of patient-reported outcomes (PROs) before stopping TKIs and after discontinuation in conjunction with Polymerase Chain Reaction (PCR) testing, though at fewer time points, utilizing online and/or phone questionnaires. Patients who have molecular CML recurrence based on RQ-PCR will restart imatinib, dasatinib, nilotinib, or bosutinib and will continue to be monitored for disease status and health status until the end of the study.
Interventions
DRUGImatinib (Stopping their TKI)
Patients with CML on treatment with imatinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years. Concurrently, the study will assess a wide range of PROs before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points, utilizing online and/or phone questionnaires.
DRUGDasatinib (Stopping their TKI)
Patients with CML on treatment with dasatinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years. Concurrently, the study will assess a wide range of PROs before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points, utilizing online and/or phone questionnaires.
DRUGNilotinib (Stopping their TKI)
Patients with CML on treatment with nilotinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years. Concurrently, the study will assess a wide range of PROs before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points, utilizing online and/or phone questionnaires.
DRUGBosutinib (Stopping their TKI)
Patients with CML on treatment with bosutinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years. Concurrently, the study will assess a wide range of PROs before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points, utilizing online and/or phone questionnaires.
Sponsors
University of Chicago
University of California, San Francisco
University of Utah
Dana-Farber Cancer Institute
Emory University
Barbara Ann Karmanos Cancer Institute
Duke Cancer Institute
Fred Hutchinson Cancer Center
Memorial Sloan Kettering Cancer Center
Weill Medical College of Cornell University
H. Lee Moffitt Cancer Center and Research Institute
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 or older at time of study entry 2. Willing and able to give informed consent 3. Diagnosed with CML in chronic phase and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR-ABL protein 4. Currently taking imatinib, dasatinib, nilotinib or bosutinib 5. Patient has been on TKI therapy for at least 3 years 6. Documented BCR-ABL \<0.01% (\>MR4 i.e. \>4 log reduction) or undetectable BCR-ABL by PCR for at least 2 years according to the patient's local lab 7. Documented BCR-ABL \<0.01% (\>MR4 i.e. \>4 log reduction) or undetectable BCR-ABL at least 3 times prior to screening according to the patient's local lab 8. Two (2) Screening PCRs have been completed and both results are \< 0.01% (\>MR4 i.e \> 4 log reduction) by central lab 9. Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed) 10. Patient has been compliant with therapy per treating physician
Exclusion criteria
1. Prior hematopoietic stem cell transplantation 2. Poor compliance with taking TKI 3. Unable to comply with lab appointments schedule and PRO assessments 4. Life expectancy less than 36 months 5. Patients who have been resistant to previous TKI therapy are not eligible 6. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36 months | The number of patients who develop molecular recurrence after discontinuing TKIs. This will be reported as the number of new occurrences from the end of the prior time frame. |
| Patient-reported Health Status Related to Fatigue of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | Baseline | Patient-reported health status of fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. The research team used five questions. The responses are in a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric for interpretation of results. The mean score for a relevant reference population (United States general population in this case) is 50 and 10 is the standard deviation of that population. T-score range is 20 to 80. Thus, a score of 40 is one standard deviation lower than the reference population mean and a score of 60 is one standard deviation higher than the reference population mean. Higher scores for this scale are indicative of worse symptoms. |
| Patient-reported Health Status Related to Fatigue of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | Six months | Patient-reported health status of fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. The research team used five questions. The responses are in a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric for interpretation of results. The mean score for a relevant reference population (United States general population in this case) is 50 and 10 is the standard deviation of that population. T-score range is 20 to 80. Thus, a score of 40 is one standard deviation lower than the reference population mean and a score of 60 is one standard deviation higher than the reference population mean. Higher scores for this scale are indicative of worse symptoms. |
| Patient-reported Health Status Related to Diarrhea of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | Baseline | Patient-reported health status of diarrhea using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are two unrelated questions. Question no. 1 focuses on loose or watery stool and asks how many days the subject experienced this. O is no days and 4 is six to seven days. Question no. 2 asks if the subject often feels the need to empty the bowel right away. Responses are 0 (never) to 4 (more than once a day). Responses are a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms. |
| Patient-reported Health Status Related to Diarrhea of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | Six months | Patient-reported health status of diarrhea using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are two unrelated questions. Question no. 1 focuses on loose or watery stool and asks how many days the subject experienced this. O is no days and 4 is six to seven days. Question no. 2 asks if the subject often feels the need to empty the bowel right away. Responses are 0 (never) to 4 (more than once a day). Responses are a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms. |
| Patient-reported Health Status Related to Sleep Status of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | Baseline | Patient-reported health status of sleep using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are four questions. The responses are in a Likert Scale numbered one to five. All questions are regarding the quality of sleep. The answers are one (not at all) to 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms. |
| Patient-reported Health Status Related to Sleep Status of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | Six months | Patient-reported health status of sleep using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are four questions. The responses are in a Likert Scale numbered one to five. All questions are regarding the quality of sleep. The answers are one (not at all) to 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Discontinuation of TKI Medication Patients with CML on treatment with imatinib, dasatinib, nilotinib, or bosutinib and are in confirmed deep molecular response will stop their TKI. Confirmed deep (\> 4 log reduction) molecular response (\>MR4) defined as p210 (bcr-abl) fusion protein (BCR-ABL) \< 0.01%, for at least two years.
Concurrently, the study will assess a wide range of PROs before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points, utilizing online and/or phone questionnaires. | 172 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
Baseline characteristics
| Characteristic | Discontinuation of TKI Medication |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 49 Participants |
| Age, Categorical Between 18 and 65 years | 123 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 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 | 17 Participants |
| Race (NIH/OMB) White | 139 Participants |
| Region of Enrollment United States | 172 participants |
| Sex: Female, Male Female | 89 Participants |
| Sex: Female, Male Male | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 173 |
| other Total, other adverse events | 173 / 173 |
| serious Total, serious adverse events | 5 / 173 |
Outcome results
Primary
Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs.
The number of patients who develop molecular recurrence after discontinuing TKIs. This will be reported as the number of new occurrences from the end of the prior time frame.
Time frame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36 months
Population: One subject expired after the 10th month visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Four months to five months | 7 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 18 months to 20 months | 0 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 20 months to 22 months | 0 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 22 months to 24 months | 1 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Less or equal to one month | 0 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | One month to two months | 4 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Two months to three months | 12 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Three months to four months | 11 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Five months to six months | 5 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Six months to eight months | 2 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Eight months to 10 months | 3 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | Ten months to 12 months | 4 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 12 months to 14 months | 2 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 14 months to 16 months | 2 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 16 months to 18 months | 1 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 24 months to 27 months | 1 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 27 months to 30 months | 2 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 30 months to 33 months | 0 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 33 months to 36 months | 0 Participants |
| Discontinuation of TKI Medication | Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs. | 36 months | 2 Participants |
Primary
Patient-reported Health Status Related to Diarrhea of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of diarrhea using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are two unrelated questions. Question no. 1 focuses on loose or watery stool and asks how many days the subject experienced this. O is no days and 4 is six to seven days. Question no. 2 asks if the subject often feels the need to empty the bowel right away. Responses are 0 (never) to 4 (more than once a day). Responses are a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms.
Time frame: Six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Diarrhea of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | 40.8 T-Score | Standard Deviation 9.2 |
Primary
Patient-reported Health Status Related to Diarrhea of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of diarrhea using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are two unrelated questions. Question no. 1 focuses on loose or watery stool and asks how many days the subject experienced this. O is no days and 4 is six to seven days. Question no. 2 asks if the subject often feels the need to empty the bowel right away. Responses are 0 (never) to 4 (more than once a day). Responses are a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Diarrhea of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | 43.6 T-Score | Standard Deviation 8.3 |
Primary
Patient-reported Health Status Related to Fatigue of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. The research team used five questions. The responses are in a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric for interpretation of results. The mean score for a relevant reference population (United States general population in this case) is 50 and 10 is the standard deviation of that population. T-score range is 20 to 80. Thus, a score of 40 is one standard deviation lower than the reference population mean and a score of 60 is one standard deviation higher than the reference population mean. Higher scores for this scale are indicative of worse symptoms.
Time frame: Six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Fatigue of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | 50.2 T-Score | Standard Deviation 11.1 |
Primary
Patient-reported Health Status Related to Fatigue of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. The research team used five questions. The responses are in a Likert -style scale numbered one to five -- 1 (not at all) and 5 (very much). PROMIS scales use a T-score metric for interpretation of results. The mean score for a relevant reference population (United States general population in this case) is 50 and 10 is the standard deviation of that population. T-score range is 20 to 80. Thus, a score of 40 is one standard deviation lower than the reference population mean and a score of 60 is one standard deviation higher than the reference population mean. Higher scores for this scale are indicative of worse symptoms.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Fatigue of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | 52.9 T-Score | Standard Deviation 9.9 |
Primary
Patient-reported Health Status Related to Sleep Status of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of sleep using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are four questions. The responses are in a Likert Scale numbered one to five. All questions are regarding the quality of sleep. The answers are one (not at all) to 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms.
Time frame: Six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Sleep Status of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs) | 48.3 T-Score | Standard Deviation 9.6 |
Primary
Patient-reported Health Status Related to Sleep Status of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
Patient-reported health status of sleep using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales. There are four questions. The responses are in a Likert Scale numbered one to five. All questions are regarding the quality of sleep. The answers are one (not at all) to 5 (very much). PROMIS scales use a T-score metric interpret results. The mean score for a relevant reference population (United States general population) is 50 and 10 is the standard deviation of the population. T-score range is 20 to 80. A score of 40 is one standard deviation lower than the reference population mean and 60 is one standard deviation higher than the reference population mean. Higher scores indicate worse symptoms.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Discontinuation of TKI Medication | Patient-reported Health Status Related to Sleep Status of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs) | 49.7 T-Score | Standard Deviation 8.2 |