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

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02269267
• Collaborator: University of Chicago (Other), University of California, San Francisco (Other), University of Utah (Other), Dana-Farber Cancer Institute (Other), Emory University (Other), Barbara Ann Karmanos Cancer Institute (Other), Duke Cancer Institute (Other), Fred Hutchinson Cancer Center (Other), Memorial Sloan Kettering Cancer Center (Other), Weill Medical College of Cornell University (Other), H. Lee Moffitt Cancer Center and Research Institute (Other)
• Enrollment: 173
• Locations: 16
• Anticipated Duration (Months): 95.4
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Chronic	Other: Stopping their TKI

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 173 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)
• Actual Study Start Date: Dec 18, 2014
• Actual Primary Completion Date: Dec 1, 2021
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm

Intervention/Treatment

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.

Other: 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. 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.

Outcome Measures

Primary Outcome Measures

1. Proportion of patients with 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.

2. Patient-reported health status related to fatigue of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

3. Patient-reported health status related to depression of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of depression using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

4. Patient-reported health status related to sleep of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of sleep using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

5. Patient-reported health status related to GI symptoms of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of GI symptoms using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

6. Patient-reported health status related to anxiety of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of anxiety symptoms using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

7. Patient-reported health status related to physical function of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of physical function symptoms using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

8. Patient-reported health status related to pain of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of pain symptoms using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

9. Patient-reported health status related to social function of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

   Patient-reported health status of social function using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

10. Patient-reported health status related to sexual function of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

    Patient-reported health status of sexual function using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

11. Patient-reported health status related to social isolation of patients before and after stopping TKIs [Before and 3 years stopping TKIs.]

    Patient-reported health status of social isolation using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

12. Patient-reported health status related to cognitive function of patients before and after stopping TKIs. [Before and 3 years stopping TKIs.]

    Patient-reported health status of cognitive function using the Patient-Reported Outcomes Measurement Information System (PROMIS) scales.

13. Patient-reported health status. [Before and 3 years stopping TKIs.]

    In outcomes two through 12, if the PROMIS scale cannot be used, then the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) -CML Symptom Burden scale will be used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Helen Diller Family Comprehensive Cancer Center University of California	San Francisco	California	United States	94143
2	Moffit Cancer Center	Tampa	Florida	United States	33612
3	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
4	The University of Chicago	Chicago	Illinois	United States	60637
5	The University of Chicago Medicine Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
6	Beth Israel Deaconess Medical Center (Satellite site of Dana Farber)	Boston	Massachusetts	United States	02215
7	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Karmanos Cancer Institute of Wayne State University	Detroit	Michigan	United States	48201
9	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
10	Weill Medical College of Cornell University	New York	New York	United States	10021
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
12	Duke University Medical Center	Durham	North Carolina	United States	27710
13	MD Anderson Cancer Center	Houston	Texas	United States	77054
14	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132-2408
15	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
16	Froedtert Hospital & Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Medical College of Wisconsin
• 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

Investigators

• Principal Investigator: Ehab Atallah, MD, Medical College of Wisconsin
• Principal Investigator: Kathryn Flynn, PhD, Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ehab L Atallah, Professor (Principal Investigator), Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT02269267
• Other Study ID Numbers: PRO00023447
• First Posted: Oct 21, 2014
• Last Update Posted: Jan 12, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Tin Fluorides

Study Results

No Results Posted as of Jan 12, 2022