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.
Active, not recruiting
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Proportion of patients with CML who develop molecular recurrence after discontinuing TKIs |
| Time Frame: | 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36 months |
| Safety Issue: | |
| Description: | The number of patients who develop molecular recurrence after discontinuing TKIs. |
| Phase: | |
| Primary Purpose: | Observational |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Medical College of Wisconsin |
December 19, 2020
