The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)

Phase 2

Completed

Conditions: Leukemia, Myeloid, Chronic

Interventions: Drug: Imatinib (Stopping their TKI)
Drug: Dasatinib (Stopping their TKI)
Drug: Nilotinib (Stopping their TKI)
Drug: Bosutinib (Stopping their TKI)

Registration Number: NCT02269267

Lead Sponsor: Medical College of Wisconsin

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 173

Inclusion Criteria

Age 18 or older at time of study entry
Willing and able to give informed consent
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
Currently taking imatinib, dasatinib, nilotinib or bosutinib
Patient has been on TKI therapy for at least 3 years
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
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
Two (2) Screening PCRs have been completed and both results are < 0.01% (>MR4 i.e > 4 log reduction) by central lab
Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed)
Patient has been compliant with therapy per treating physician

Exclusion Criteria

Prior hematopoietic stem cell transplantation
Poor compliance with taking TKI
Unable to comply with lab appointments schedule and PRO assessments
Life expectancy less than 36 months
Patients who have been resistant to previous TKI therapy are not eligible
Pregnant or lactating women

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Discontinuation of TKI medication	Imatinib (Stopping their TKI)	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.
Discontinuation of TKI medication	Bosutinib (Stopping their TKI)	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.
Discontinuation of TKI medication	Nilotinib (Stopping their TKI)	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.
Discontinuation of TKI medication	Dasatinib (Stopping their TKI)	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.

Primary Outcome Measures

Name	Time	Method
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 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.
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 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 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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (16): MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Moffit Cancer Center
🇺🇸
Tampa, Florida, United States
Beth Israel Deaconess Medical Center (Satellite site of Dana Farber)
🇺🇸
Boston, Massachusetts, United States
Karmanos Cancer Institute of Wayne State University
🇺🇸
Detroit, Michigan, United States
University of Utah Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
Froedtert Hospital & Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
The University of Chicago
🇺🇸
Chicago, Illinois, United States
Helen Diller Family Comprehensive Cancer Center University of California
🇺🇸
San Francisco, California, United States
Winship Cancer Institute of Emory University
🇺🇸
Atlanta, Georgia, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
The University of Chicago Medicine Comprehensive Cancer Center at Silver Cross
🇺🇸
New Lenox, Illinois, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Weill Medical College of Cornell University
🇺🇸
New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States