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

Medical College of Wisconsin

Status and phase: Completed; Phase 2

Conditions: Leukemia, Myeloid, Chronic

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02269267

PRO00023447

Details and patient eligibility

About

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.

Full 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.

Enrollment: 173 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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173 participants in 1 patient group

Discontinuation of TKI medication

Other group

Description:

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.

Treatment:

Drug: Bosutinib (Stopping their TKI)

Drug: Imatinib (Stopping their TKI)

Drug: Dasatinib (Stopping their TKI)

Drug: Nilotinib (Stopping their TKI)