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

NCT ID: NCT02269267

Last Updated: 2023-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-18
• Study Completion Date: 2022-04-06

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.

Conditions

Leukemia, Myeloid, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Imatinib (Stopping their TKI)

Intervention Type: 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.

Dasatinib (Stopping their TKI)

Intervention Type: 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.

Nilotinib (Stopping their TKI)

Intervention Type: 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.

Bosutinib (Stopping their TKI)

Intervention Type: 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.

Interventions

Imatinib (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.

Intervention Type: DRUG

Dasatinib (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.

Intervention Type: DRUG

Nilotinib (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.

Intervention Type: DRUG

Bosutinib (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.

Intervention Type: DRUG

Other Intervention Names

Gleevec; Sprycel; Tasigna; BOSULIF

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: collaborator

Duke Cancer Institute

OTHER

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Ehab L Atallah

Professor (Principal Investigator)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ehab Atallah, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Kathryn Flynn, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Helen Diller Family Comprehensive Cancer Center University of California

San Francisco, California, United States

Moffit Cancer Center

Tampa, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

The University of Chicago

Chicago, Illinois, United States

The University of Chicago Medicine Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

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

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute of Wayne State University

Detroit, Michigan, 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

Duke University Medical Center

Durham, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Froedtert Hospital & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 29609532 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33180106 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO00023447

Identifier Type: -

Identifier Source: org_study_id