Leukemia, Myelogenous, Chronic, BCR-ABL PositiveTAKE-ITNCT01768689
Interventional Study to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
A study testing Adherence-encouraging interventions - Group meeting, Adherence-encouraging interventions - Individual meetings and Adherence-encouraging interventions - Monthly phone calls in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive and Medication Adherence, run by pia raanani at 4 sites in Israel.
Trial summary
Adherence to tyrosine kinase inhibitors is associated with improved outcomes in chronic myeloid leukemia patients. Hence, improved adherence might improve CML patients' prognosis. Decreased adherence is a common problem in such patients, with non-adherence in up to 30% of patients in several studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Medication Adherence
- What is being tested?
- Adherence-encouraging interventions - Group meeting, Adherence-encouraging interventions - Individual meetings and Adherence-encouraging interventions - Monthly phone calls
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 4 sitesIsrael
- Study dates
- Oct 2013to Jun 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with chronic phase chronic myeloid leukemia (CP-CML), aged 18 years or older
- CP-CML defined as: Medical history of cytogenetically confirmed CP-CML defined as the presence of the Philadelphia chromosome on bone marrow aspirates (a minimum of 20 metaphases is required; FISH cannot be used). If Philadelphia chromosome was negative or if cytogenetic results were not available, BCR-ABL-positive CML patients can be included.
- At least 3 months of TKI treatment (imatinib, dasatinib or nilotinib) before study initiation.
Who cannot join
- Current or prior accelerated/blast phase or stem cell transplant
- Participation in another interventional study
- Pregnancy
Trial locations and contacts
4 sites in 1 country.
Israel4 sites
Soroka Medical Center
Beersheba, 84101
Rambam Medical Center
Haifa
Meir Medical Center
Kfar Saba, 44281
Rabin Medical Center
Petah Tikva, 49100
About this study
Official title: The Effect of Active Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - A Prospective Observational Multicenter Study (TAKE-IT)
Adherence to tyrosine kinase inhibitors is associated with improved outcomes in chronic myeloid leukemia patients. Hence, improved adherence might improve CML patients' prognosis.
Decreased adherence is a common problem in such patients, with non-adherence in up to 30% of patients in several studies. Recently, an emphasis has been placed on improving patient's adherence to tyrosine kinase inhibitors in these patients. However, there is no prospective high-quality evidence showing that adherence can be improved in these patients.
Therefore, the investigators hypothesize that adherence-encouraging interventions improve adherence to tyrosine kinase inhibitors in chronic myeloid leukemia patients.
Read the detailed description
The cytogenetic hallmark of chronic myeloid leukemia (CML) is the reciprocal translocation between chromosomes 9 and 22 creating the Philadelphia (Ph(1)) chromosome. The BCRABL1 fusion gene is the result of this translocation and encodes for a constitutively active tyrosine kinase responsible for the development of CML. Tyrosine kinase inhibitors (TKIs) targeting the protein product of this aberrant gene, the BCRABL-1 protein, have revolutionized the therapeutic approach to chronic myeloid leukemia (CML). Treatment with the first FDA approved TKI, imatinib mesylate (Gleevec, Novartis), in chronic phase CML results in a projected 8 year overall survival of 85%. Recently, two second generation TKIs, Dasatinib and Nilotinib, have been approved for use in newly diagnosed chronic phase CML, as a result of studies showing improved molecular and cytogenetic outcomes. Importantly, in each of the above studies there was a substantial number of dropouts due to drug intolerance and resistance, among other reasons. In a prospective observational study of 169 CML patients, only 14% of patients were fully adherent with prescribed imatinib. Moreover, one third of patients were considered to be non-adherent, which is similar to the proportion of dropouts in the landmark studies on TKIs in CML. Thus, it is clear that there is a subgroup of patients who do not properly adhere to treatment. This is especially significant because the contemporary approach to CML in complete cytogenetic remission (CCyR) and major molecular remission (MMR) necessitates long-term, chronic treatment with TKIs.
Therefore, although hematologists have the luxury of an armamentarium of highly effective drugs, one of the most challenging aspects of treating CML is the management of non-compliance to TKI treatment. TKI-induced adverse effects are only one of a wide spectrum of reasons for non-adherence to TKI treatment.
Recently several studies have demonstrated the prognostic importance of adhering to imatinib treatment. In a pivotal study of 87 chronic phase CML (CP-CML) patients in CCyR, an adherence rate of > 90% strongly correlated with the 6 year probability of achieving MMR (94.5% vs. 28.4% when adherence rates were ≤ 90%). Non-adherence to imatinib treatment also adversely affects event free survival and is associated with loss of CCyR in patients on long term treatment. These data support the intuitive concept that CML can be effectively treated with the drugs currently available, as long as patients adhere to treatment. Moreover, non-adherence to imatinib treatment has been associated with increased economic burden and healthcare costs. Consequently, TKI adherence is an attractive potential target for intervention.
Non-adherence to medication is an intricate problem that is influenced by the physician, the healthcare system, and economic and social factors. Other medical disciplines have assessed various modes of improving adherence to therapeutic regimens, with varying success. A recent study assessing adherence-related behavior among CML patients, demonstrated that among a multitude of reasons for non-adherence, patient forgetfulness and drug side effects were the most common causes of unintentional and intentional non-adherence, respectively. Several methods of improving adherence among patients with CML were retrospectively assessed by Moon et al. Subjects in the intervention arm were more likely to receive prescriptions for imatinib than those receiving standard care (98.2 ± 0.03% vs. 79.3 ± 0.16%). Although there was no difference in adherence to prescribed treatment between the two groups, the overall compliance, a composite endpoint of the above two outcomes, was markedly improved in the intervention group ((93.0 ± 2.3% vs. 76.2 ± 7.4%, P = 0.001). Recently, Gater et al conceived a conceptual model aimed at improving adherence in CML patients treated with 1st and 2nd generation TKIs, based on a systematic review of the literature. However, there are currently no prospective data evaluating whether adherence in CML can be influenced by active intervention.
Study Hypothesis:
Adherence to tyrosine kinase inhibitors (TKIs) is associated with improved outcomes in chronic myeloid leukemia (CML) patients. Hence, improved adherence might improve CML patients' prognosis.
The investigators hypothesize that adherence-encouraging interventions improve adherence to TKIs in CML patients.
Study Objective:
- Primary Objective: By means of a prospective before-after study, the investigators aim to assess whether specific adherence-encouraging interventions improve TKI adherence in patients with CP-CML treated by these agents. The investigators will target previously documented reasons for non-adherence 11 with interventions that were selected based on prior experience in other medical disciplines and will evaluate their contribution to patients' adherence to treatment.
- To better understand non-adherence in CML and pinpoint independent risk factors for non-adherence
- To validate questionnaires assessing adherence, and evaluate whether they could be of use in indentifying patients at risk for non-adherence
- To compare adherence to second generation TKIs with adherence to imatinib
- To assess the role of a clinical pharmacist in preventing potential drug interactions
- To determine whether the intervention has a long term effect on adherence during one year of post-intervention follow up
- To estimate long term effects of adherence on clinical, cytogenetic and molecular outcomes
- Being tested
- Adherence-encouraging interventions - Group meeting, Adherence-encouraging interventions - Individual meetings, Adherence-encouraging interventions - Monthly phone calls
- Keywords
- adherence, chronic myeloid leukemia, tyrosine kinase inhibitors
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Medication Adherence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adherence-encouraging interventions - Group meetingBehavioural
One Group meeting (at the beginning of the intervention period) for all participants, focusing on issues relevant to adherence improvement
Adherence-encouraging interventions - Individual meetingsBehavioural
Individual meetings focusing on adherence issues with a multidiscilinary team
Adherence-encouraging interventions - Monthly phone callsBehavioural
Monthly phone calls to detect urgent adherence-related issues
| Study group | Role | What they receive |
|---|---|---|
| Run-in period | No intervention | First 3 months of study during which adherence will be measured for each consecutively included study subject, but no intervention will be performed. Patient will receive routine treatment for CML according to the physician discretion. |
| Adherence-encouraging period | Experimental | Months 4 to 9 of study during which adherence will be measured for each consecutively included study subject, while implementing adherence-encouraging interventions:
1. adherence-encouraging interventions - Group meetings
2. adherence-encouraging interventions - Individual meetings
3. adherence-encouraging interventions - Monthly phone calls
Patient will receive routine treatment for CML according to the physician discretion. Receives: Behavioral: Adherence-encouraging interventions - Group meeting; Behavioral: Adherence-encouraging interventions - Individual meetings; Behavioral: Adherence-encouraging interventions - Monthly phone calls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinically relevant change in MEMS-measured adherence
Improvement in a patient's adherence from less than 90% during the initial 3 month run-in period, to 90% or more during the first 3 months of intervention.
Definitions:
- Adherence above 90% was defined as clinically relevant.
- Adherence rate = actual calculated dose/prescribed dose.
- Adherence will be calculated from "medical events monitoring system" (MEMS) data which will be collected continuously throughout the first 7.5 months of the study period. MEMS is an electronic monitoring system designed to compile the dosing histories of ambulatory patients prescribed oral medications
Measured: From 3 months before intervention, until 3 months after starting the intervention
General improvement in MEMS-measured adherence
An absolute improvement of 10% in a patient's adherence, between their adherence during the initial 3 month run-in period and their adherence during the first 3 months of intervention.
See Definitions of adherence rate and measurement of adherence in the first primary outcome description.
Measured: 3 months prior to the intervention, until 3 months after starting the intervention
Secondary outcomes (7)
Mean-difference in MEMS-measured adherence
Mean-difference in adherence (as measured by the MEMS) between the run-in period and the first 3 months of the intervention period (paired t-test).
The aim is to evaluate whether such a difference exists and whether it has statistical significance.
For more details on the MEMS system, please see the description under the primary outcome.
Measured: 3 months prior to intervention until 3 months after starting the intervention
Mean change in The Basel Assessment of Adherence to Tyrosine Kinase Inhibitors Scale (BAATIS)
Mean-difference in BAATIS scale scores between the run-in period and the intervention period (paired t-test)
The BAATIS is a clinician reported outcome which has been used to assess adherence to immunosuppressive medication in solid organ transplant patients (BAASIS; Basal assessment of adherence with the Immunosuppressive Regimen Scale). Noens et al adapted the questionnaire for use among CML patients in the ADAGIO study. We have performed a similar adaptation
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
Measured: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Effect of intervention on tyrosine kinase inhibtor related adverse events
The incidence of tyrosine kinase inhibitor related adverse events during 6 months of intervention compared to that witnessed during the initial 3 month run-in period
Measured: 3 months prior to intervention until 6 months after starting the intervention
Adverse effects of tyrosine kinase inhibitors as a measure of MEMS-measured adherence
The incidence of tyrosine kinase inhibtor related adverse events throughout the first 6 months of the study period as a function of adherence (measured by MEMS)
Measured: 3 months prior to intervention until 3 months after starting the intervention
Percentage of patients improving in patient self-reported non-adherence
The percentage of patients changing from a self-reported non-adherence of "yes" during the run-in period, to a self-reported non-adherence of "no" after the intervention, compared to the percentage of those who answered "yes" during the study period and remained "yes" after the intervention.
Definition of the "Patient self-reported question regarding non-adherence":
Each patient is asked the following question:
"It is common that patients at times miss a few doses, for a whole range of reasons. Thinking of the past 7 days have you missed any doses?"
If a patient answers 'yes' it will be taken as an indication that the patient has problems with adherence.
Measured: 3 months prior to intervention until 6 months after starting the intervention
Mean change in the physician visual analogue scale (VAS) of adherence
Mean-difference in physician visual analogue scale (VAS) of adherence scores between the run-in period and the intervention period (paired t-test).
The physician VAS on adherence rates patient adherence (as assessed by a physician) on a 10 cm VAS scale. A similar scale is in widespread use in several clinical disciplines, especially in assessing pain. It has also been used in assessing adherence to medication.
The VAS ranges from perfect adherence (100% = 100mm) to no adherence (0% = 0mm).
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
Measured: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Mean change in the patient visual analogue scale (VAS) of adherence
Mean-difference in patient visual analogue scale (VAS) of adherence scores between the run-in period and the intervention period (paired t-test).
The patient VAS on adherence rates patient adherence (as assessed by the patient) on a 10 cm VAS scale.
See detailed explanation on the VAS under the outcome "Mean change in the physician visual analogue scale (VAS) of adherence"
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
Measured: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2013 (estimated)
- Study startOct 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myelogenous, Chronic, BCR-ABL PositiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- pia raanani
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, pia raanani, Rabin Medical Center
- Investigators
- Pia Raanani, MD, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01768689
- Sponsor's protocol ID
- TAKE IT - CML adherence
- Acronym
- TAKE-IT
- Status last verified
- Jun 2017
- First submitted
- 8 Jan 2013
- Last updated
- 7 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Noens L, van Lierde MA, De Bock R, Verhoef G, Zachee P, Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonald K, De Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009 May 28;113(22):5401-11. doi: 10.1182/blood-2008-12-196543. Epub 2009 Apr 6.
PubMed 19349618Eliasson L, Clifford S, Barber N, Marin D. Exploring chronic myeloid leukemia patients' reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leuk Res. 2011 May;35(5):626-30. doi: 10.1016/j.leukres.2010.10.017. Epub 2010 Nov 20.
PubMed 21095002Gater A, Heron L, Abetz-Webb L, Coombs J, Simmons J, Guilhot F, Rea D. Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia. Leuk Res. 2012 Jul;36(7):817-25. doi: 10.1016/j.leukres.2012.01.021. Epub 2012 Feb 23.
PubMed 22364811Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, Apperley JF, Szydlo R, Desai R, Kozlowski K, Paliompeis C, Latham V, Foroni L, Molimard M, Reid A, Rezvani K, de Lavallade H, Guallar C, Goldman J, Khorashad JS. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010 May 10;28(14):2381-8. doi: 10.1200/JCO.2009.26.3087. Epub 2010 Apr 12.
PubMed 20385986Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. doi: 10.1056/NEJMra050100. No abstract available.
PubMed 16079372Moon JH, Sohn SK, Kim SN, Park SY, Yoon SS, Kim IH, Kim HJ, Kim YK, Min YH, Cheong JW, Kim JS, Jung CW, Kim DH. Patient counseling program to improve the compliance to imatinib in chronic myeloid leukemia patients. Med Oncol. 2012 Jun;29(2):1179-85. doi: 10.1007/s12032-011-9926-8. Epub 2011 Apr 7.
PubMed 21472487Jonsson S, Olsson B, Soderberg J, Wadenvik H. Good adherence to imatinib therapy among patients with chronic myeloid leukemia--a single-center observational study. Ann Hematol. 2012 May;91(5):679-685. doi: 10.1007/s00277-011-1359-0. Epub 2011 Nov 3.
PubMed 22048790
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Active Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - A Prospective Observational Multicenter Study (TAKE-IT)
- ClinicalTrials.gov ID
- NCT01768689
- Acronym / sponsor ID
- TAKE-IT / TAKE IT - CML adherence
- Keywords
- adherence, chronic myeloid leukemia, tyrosine kinase inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- pia raananiUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 15 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adherence to tyrosine kinase inhibitors is associated with improved outcomes in chronic myeloid leukemia patients. Hence, improved adherence might improve CML patients' prognosis.
Decreased adherence is a common problem in such patients, with non-adherence in up to 30% of patients in several studies. Recently, an emphasis has been placed on improving patient's adherence to tyrosine kinase inhibitors in these patients. However, there is no prospective high-quality evidence showing that adherence can be improved in these patients.
Therefore, the investigators hypothesize that adherence-encouraging interventions improve adherence to tyrosine kinase inhibitors in chronic myeloid leukemia patients.
Detailed description
The cytogenetic hallmark of chronic myeloid leukemia (CML) is the reciprocal translocation between chromosomes 9 and 22 creating the Philadelphia (Ph(1)) chromosome. The BCRABL1 fusion gene is the result of this translocation and encodes for a constitutively active tyrosine kinase responsible for the development of CML. Tyrosine kinase inhibitors (TKIs) targeting the protein product of this aberrant gene, the BCRABL-1 protein, have revolutionized the therapeutic approach to chronic myeloid leukemia (CML). Treatment with the first FDA approved TKI, imatinib mesylate (Gleevec, Novartis), in chronic phase CML results in a projected 8 year overall survival of 85%. Recently, two second generation TKIs, Dasatinib and Nilotinib, have been approved for use in newly diagnosed chronic phase CML, as a result of studies showing improved molecular and cytogenetic outcomes. Importantly, in each of the above studies there was a substantial number of dropouts due to drug intolerance and resistance, among other reasons. In a prospective observational study of 169 CML patients, only 14% of patients were fully adherent with prescribed imatinib. Moreover, one third of patients were considered to be non-adherent, which is similar to the proportion of dropouts in the landmark studies on TKIs in CML. Thus, it is clear that there is a subgroup of patients who do not properly adhere to treatment. This is especially significant because the contemporary approach to CML in complete cytogenetic remission (CCyR) and major molecular remission (MMR) necessitates long-term, chronic treatment with TKIs.
Therefore, although hematologists have the luxury of an armamentarium of highly effective drugs, one of the most challenging aspects of treating CML is the management of non-compliance to TKI treatment. TKI-induced adverse effects are only one of a wide spectrum of reasons for non-adherence to TKI treatment.
Recently several studies have demonstrated the prognostic importance of adhering to imatinib treatment. In a pivotal study of 87 chronic phase CML (CP-CML) patients in CCyR, an adherence rate of > 90% strongly correlated with the 6 year probability of achieving MMR (94.5% vs. 28.4% when adherence rates were ≤ 90%). Non-adherence to imatinib treatment also adversely affects event free survival and is associated with loss of CCyR in patients on long term treatment. These data support the intuitive concept that CML can be effectively treated with the drugs currently available, as long as patients adhere to treatment. Moreover, non-adherence to imatinib treatment has been associated with increased economic burden and healthcare costs. Consequently, TKI adherence is an attractive potential target for intervention.
Non-adherence to medication is an intricate problem that is influenced by the physician, the healthcare system, and economic and social factors. Other medical disciplines have assessed various modes of improving adherence to therapeutic regimens, with varying success. A recent study assessing adherence-related behavior among CML patients, demonstrated that among a multitude of reasons for non-adherence, patient forgetfulness and drug side effects were the most common causes of unintentional and intentional non-adherence, respectively. Several methods of improving adherence among patients with CML were retrospectively assessed by Moon et al. Subjects in the intervention arm were more likely to receive prescriptions for imatinib than those receiving standard care (98.2 ± 0.03% vs. 79.3 ± 0.16%). Although there was no difference in adherence to prescribed treatment between the two groups, the overall compliance, a composite endpoint of the above two outcomes, was markedly improved in the intervention group ((93.0 ± 2.3% vs. 76.2 ± 7.4%, P = 0.001). Recently, Gater et al conceived a conceptual model aimed at improving adherence in CML patients treated with 1st and 2nd generation TKIs, based on a systematic review of the literature. However, there are currently no prospective data evaluating whether adherence in CML can be influenced by active intervention.
Study Hypothesis:
Adherence to tyrosine kinase inhibitors (TKIs) is associated with improved outcomes in chronic myeloid leukemia (CML) patients. Hence, improved adherence might improve CML patients' prognosis.
The investigators hypothesize that adherence-encouraging interventions improve adherence to TKIs in CML patients.
Study Objective:
- Primary Objective: By means of a prospective before-after study, the investigators aim to assess whether specific adherence-encouraging interventions improve TKI adherence in patients with CP-CML treated by these agents. The investigators will target previously documented reasons for non-adherence 11 with interventions that were selected based on prior experience in other medical disciplines and will evaluate their contribution to patients' adherence to treatment.
- To better understand non-adherence in CML and pinpoint independent risk factors for non-adherence
- To validate questionnaires assessing adherence, and evaluate whether they could be of use in indentifying patients at risk for non-adherence
- To compare adherence to second generation TKIs with adherence to imatinib
- To assess the role of a clinical pharmacist in preventing potential drug interactions
- To determine whether the intervention has a long term effect on adherence during one year of post-intervention follow up
- To estimate long term effects of adherence on clinical, cytogenetic and molecular outcomes
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Run-in period | No intervention | –First 3 months of study during which adherence will be measured for each consecutively included study subject, but no intervention will be performed. Patient will receive routine treatment for CML according to the physician discretion. |
| Adherence-encouraging period | Experimental | Behavioral: Adherence-encouraging interventions - Group meeting, Behavioral: Adherence-encouraging interventions - Individual meetings, Behavioral: Adherence-encouraging interventions - Monthly phone callsMonths 4 to 9 of study during which adherence will be measured for each consecutively included study subject, while implementing adherence-encouraging interventions: 1. adherence-encouraging interventions - Group meetings 2. adherence-encouraging interventions - Individual meetings 3. adherence-encouraging interventions - Monthly phone calls Patient will receive routine treatment for CML according to the physician discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with chronic phase chronic myeloid leukemia (CP-CML), aged 18 years or older
- At least 3 months of TKI treatment (imatinib, dasatinib or nilotinib) before study initiation.
Key exclusion criteria (3 listed)
- Current or prior accelerated/blast phase or stem cell transplant
- Participation in another interventional study
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adherence-encouraging interventions - Group meetingOne Group meeting (at the beginning of the intervention period) for all participants, focusing on issues relevant to adherence improvement | Behavioural | Adherence-encouraging period |
| Adherence-encouraging interventions - Individual meetingsIndividual meetings focusing on adherence issues with a multidiscilinary team | Behavioural | Adherence-encouraging period |
| Adherence-encouraging interventions - Monthly phone callsMonthly phone calls to detect urgent adherence-related issues | Behavioural | Adherence-encouraging period |
Primary outcome
Clinically relevant change in MEMS-measured adherence
Time frame: From 3 months before intervention, until 3 months after starting the intervention
Improvement in a patient's adherence from less than 90% during the initial 3 month run-in period, to 90% or more during the first 3 months of intervention. Definitions: 1. Adherence above 90% was defined as clinically relevant. 2. Adherence rate = actual calculated dose/prescribed dose. 3. Adherence will be calculated from "medical events monitoring system" (MEMS) data which will be collected continuously throughout the first 7.5 months of the study period. MEMS is an electronic monitoring system designed to compile the dosing histories of ambulatory patients prescribed oral medications
General improvement in MEMS-measured adherence
Time frame: 3 months prior to the intervention, until 3 months after starting the intervention
An absolute improvement of 10% in a patient's adherence, between their adherence during the initial 3 month run-in period and their adherence during the first 3 months of intervention. See Definitions of adherence rate and measurement of adherence in the first primary outcome description.
7 secondary outcomes
Mean-difference in MEMS-measured adherence
Time frame: 3 months prior to intervention until 3 months after starting the intervention
Mean change in The Basel Assessment of Adherence to Tyrosine Kinase Inhibitors Scale (BAATIS)
Time frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Effect of intervention on tyrosine kinase inhibtor related adverse events
Time frame: 3 months prior to intervention until 6 months after starting the intervention
Adverse effects of tyrosine kinase inhibitors as a measure of MEMS-measured adherence
Time frame: 3 months prior to intervention until 3 months after starting the intervention
Percentage of patients improving in patient self-reported non-adherence
Time frame: 3 months prior to intervention until 6 months after starting the intervention
Mean change in the physician visual analogue scale (VAS) of adherence
Time frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Mean change in the patient visual analogue scale (VAS) of adherence
Time frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Background: PubMed 19349618Noens L, van Lierde MA, De Bock R, Verhoef G, Zachee P, Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonald K, De Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009 May 28;113(22):5401-11. doi: 10.1182/blood-2008-12-196543. Epub 2009 Apr 6.
- Background: PubMed 21095002Eliasson L, Clifford S, Barber N, Marin D. Exploring chronic myeloid leukemia patients' reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leuk Res. 2011 May;35(5):626-30. doi: 10.1016/j.leukres.2010.10.017. Epub 2010 Nov 20.
- Background: PubMed 22364811Gater A, Heron L, Abetz-Webb L, Coombs J, Simmons J, Guilhot F, Rea D. Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia. Leuk Res. 2012 Jul;36(7):817-25. doi: 10.1016/j.leukres.2012.01.021. Epub 2012 Feb 23.
- Background: PubMed 20385986Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, Apperley JF, Szydlo R, Desai R, Kozlowski K, Paliompeis C, Latham V, Foroni L, Molimard M, Reid A, Rezvani K, de Lavallade H, Guallar C, Goldman J, Khorashad JS. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010 May 10;28(14):2381-8. doi: 10.1200/JCO.2009.26.3087. Epub 2010 Apr 12.
- Background: PubMed 16079372Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. doi: 10.1056/NEJMra050100. No abstract available.
- Background: PubMed 21472487Moon JH, Sohn SK, Kim SN, Park SY, Yoon SS, Kim IH, Kim HJ, Kim YK, Min YH, Cheong JW, Kim JS, Jung CW, Kim DH. Patient counseling program to improve the compliance to imatinib in chronic myeloid leukemia patients. Med Oncol. 2012 Jun;29(2):1179-85. doi: 10.1007/s12032-011-9926-8. Epub 2011 Apr 7.
- Background: PubMed 22048790Jonsson S, Olsson B, Soderberg J, Wadenvik H. Good adherence to imatinib therapy among patients with chronic myeloid leukemia--a single-center observational study. Ann Hematol. 2012 May;91(5):679-685. doi: 10.1007/s00277-011-1359-0. Epub 2011 Nov 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pia Raanani, MD principal investigator
Rabin Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Adherence-encouraging interventions - Group meeting, Adherence-encouraging interventions - Individual meetings and Adherence-encouraging interventions - Monthly phone calls in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive and Medication Adherence, run by pia raanani at 4 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically relevant change in MEMS-measured adherence (time frame: From 3 months before intervention, until 3 months after starting the intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01768689, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.