Clinical trial NCT02269267: The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)
Official title: The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Chronic
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: University of Chicago
name: University of California, San Francisco
name: University of Utah
name: Dana-Farber Cancer Institute
name: Emory University
name: Barbara Ann Karmanos Cancer Institute
name: Duke Cancer Institute
name: Fred Hutchinson Cancer Center
name: Memorial Sloan Kettering Cancer Center
name: Weill Medical College of Cornell University
name: H. Lee Moffitt Cancer Center and Research Institute
First posted: 2014-10-21
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Chronic Myeloid Leukemia (CML) Who Develop Molecular Recurrence After Discontinuing TKIs.
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36 months
measure: Patient-reported Health Status Related to Fatigue of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Baseline
measure: Patient-reported Health Status Related to Fatigue of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Six months
measure: Patient-reported Health Status Related to Diarrhea of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Baseline
measure: Patient-reported Health Status Related to Diarrhea of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Six months
measure: Patient-reported Health Status Related to Sleep Status of Patients at Baseline (Before Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Baseline
measure: Patient-reported Health Status Related to Sleep Status of Patients at 6 Months (After Stopping Tyrosine Kinase Inhibitors (TKIs)
timeFrame: Six months
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Helen Diller Family Comprehensive Cancer Center University of California
state: California
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: New Lenox
country: United States
facility: The University of Chicago Medicine Comprehensive Cancer Center at Silver Cross
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Satellite site of Dana Farber)
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute of Wayne State University
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Ehab Atallah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Kathryn Flynn, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atallah E, Schiffer CA, Weinfurt KP, Zhang MJ, Radich JP, Oehler VG, Pinilla-Ibarz J, Deininger MWN, Lin L, Larson RA, Mauro MJ, Moore JO, Ritchie EK, Shah NP, Silver RT, Wadleigh M, Cortes J, Thompson J, Guhl J, Horowitz MM, Flynn KE. Design and rationale for the life after stopping tyrosine kinase inhibitors (LAST) study, a prospective, single-group longitudinal study in patients with chronic myeloid leukemia. BMC Cancer. 2018 Apr 2;18(1):359. doi: 10.1186/s12885-018-4273-1.
citation: Atallah E, Schiffer CA, Radich JP, Weinfurt KP, Zhang MJ, Pinilla-Ibarz J, Kota V, Larson RA, Moore JO, Mauro MJ, Deininger MWN, Thompson JE, Oehler VG, Wadleigh M, Shah NP, Ritchie EK, Silver RT, Cortes J, Lin L, Visotcky A, Baim A, Harrell J, Helton B, Horowitz M, Flynn KE. Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. JAMA Oncol. 2021 Jan 1;7(1):42-50. doi: 10.1001/jamaoncol.2020.5774.