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

NCT02269267 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO00023447
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 16

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.

Conditions

Leukemia, Myeloid, Chronic

Outcome Measures

Primary Outcomes (7)

• 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.

  1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36 months

• 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.

  Baseline

• 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.

  Six months

• 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.

  Baseline

• 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.

  Six months

• 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.

  Baseline

• 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.

  Six months

Study Arms (1)

Discontinuation of TKI medication

OTHER

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.

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

Interventions

Imatinib (Stopping their TKI) DRUG

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.

Also known as: Gleevec

Discontinuation of TKI medication

Dasatinib (Stopping their TKI) DRUG

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.

Also known as: Sprycel

Discontinuation of TKI medication

Nilotinib (Stopping their TKI) DRUG

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.

Also known as: Tasigna

Discontinuation of TKI medication

Bosutinib (Stopping their TKI) DRUG

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.

Also known as: BOSULIF

Discontinuation of TKI medication

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• University of Chicago: collaborator
• University of California, San Francisco: collaborator
• University of Utah: collaborator
• Dana-Farber Cancer Institute: collaborator
• Emory University: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• Duke Cancer Institute: collaborator
• Fred Hutchinson Cancer Center: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Weill Medical College of Cornell University: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (16)

Helen Diller Family Comprehensive Cancer Center University of California

San Francisco, California, 94143, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

The University of Chicago Medicine Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

Beth Israel Deaconess Medical Center (Satellite site of Dana Farber)

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute of Wayne State University

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77054, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84132-2408, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Froedtert Hospital & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 29609532 RESULT

• 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.

  PMID: 33180106 RESULT

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; Dasatinib; nilotinib; bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Results Point of Contact

• Title: Ehab Atallah, MD
• Organization: Medical College of Wisconsin

eatallah@mcw.edu

414-805-4600

Study Officials

• Ehab Atallah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Kathryn Flynn, PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor (Principal Investigator)

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 21, 2014
• Study Start: December 18, 2014
• Primary Completion: April 6, 2021
• Study Completion: April 6, 2022
• Last Updated: March 3, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)