Clinical trial NCT02164903: LEONIDAS: Quality of Life Study in Chronic Myeloid Leukemia Patients
Official title: Mid to Long-term Quality of Life Effects Of imatiNIb Versus DASatinib in Chronic Myeloid Leukemia Patients (LEONIDAS)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Myeloid Leukemia
Keywords: Quality of Life
Chronic Myeloid Leukemia
Imatinib
Dasatinib
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
Collaborators: name: European Leukemia Net
name: CML Advocates Network
First posted: 2014-06-17
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult chronic myeloid leukemia patients in first line treatment with either dasatinib or imatinib for no more than 3 years.

Brief summary: The broad goal of this study is to investigate if differences exist (and in which areas and of what magnitude) in QoL and symptoms of patients with CML being treated with first line therapy with dasatinib versus those receiving first line therapy with imatinib. Also, an additional objective is to characterize medication-taking behavior associated with imatinib or dasatinib.

Detailed description: The development of molecular targeted therapies (i.e., oral tyrosine kinase inhibitors \[TKIs\]) to treat chronic myeloid leukemia (CML) is one of the great triumphs of modern oncology and one of the spearheads of personalized medicine. Since their introduction in 2001, the number of people living with CML has doubled, a trend that is expected to continue.

This study (i.e., LEONIDAS) is set up to generate evidence-based data and produce information that will advance scientific knowledge, clinical practice and health services management to facilitate clinical decision-making in CML.

In an effort to further promote patient-centered care for CML a patient advocacy organization, that is the: CML Advocates Network, is involved in this project with key representatives who will be in the advisory board team. The CML Advocates Network, hosted by the patient-run, non-profit Leukemia Patient Advocates Foundation is a worldwide network of 82 non-profit organizations from 63 countries supporting patients with CML and their relatives.

Rationale and Significance Some ten years ago, the treatment of CML was relatively straightforward as all patients received imatinib as first-line treatment and for those who failed imatinib, the only available proven alternative was allogeneic stem cell transplantation. Nowadays, with three effective drugs (i.e., imatinib, nilotinib and dasatinib), that can be used frontline in newly diagnosed chronic phase (CP) CML patients, treatment decision-making for individual patients in daily clinical practice has thus rapidly grown in complexity. Moreover, a new tyrosine kinase inhibitors (TKI), bosutinib, has been recently approved for as second-line treatment and undergoing clinical trials are assessing its efficacy as frontline strategy in CML.

To further complicate the scenario, is the fact that despite nilotinib and dasatinib have been shown to have higher rates of cytogenetic and molecular responses (compared to imatinib), none of these three drugs is dramatically better than the others. To illustrate, only slightly differences exist in terms of progression-free survival for nilotinib and no differences for overall survival at 24 and/or 36 months amongst imatinib, dasatinib and nilotinib.

Nevertheless, physician-reported toxicity data suggests these drugs have different toxicity profiles, with imatinib inducing a higher proportion of low-grade side effects than second generation tyrosine kinase inhibitors (TKI) (i.e. nilotinib and dasatinib).

While a wealth of biomedical and laboratory data exists on clinical efficacy of these three drugs, the impact of these from the patients' perspective, in terms of Quality of Life (QoL) and symptom burden, has been poorly investigated. No data exists on QoL of patients treated with nilotinib or dasatinib and it is not known if these drugs provide better QoL outcomes over imatinib when used as first line therapy. Such information would be critical in the current CML arena to make more informed treatment decisions. This is a significant gap in our knowledge with respect to the modern management of CML, also because, as long-term continuous exposure to the tyrosine kinase inhibitors (TKI) is necessary, even low grade side effects can heavily impact on patients' QoL.

Thus, the objective of this study is to investigate if differences exist (and in which areas and of what magnitude) in QoL and symptoms of patients with CML being treated with first line therapy with dasatinib versus those receiving first line therapy with imatinib, as well as characterizing medication-taking behavior associated with imatinib or dasatinib.

Eligibility criteria: Inclusion Criteria:

* 18 years or older at the time of study entry;
* Diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive CML confirmed by cytogenetic and/or molecular analysis;
* At least in CCyR (as documented by chromosome banding analysis of marrow cell metaphases) or in MMR (≤0.1% BCR-ABL IS)
* CP-CML Patients in first line treatment with either dasatinib or imatinib for no more than 3 years;
* Written informed consent.

Exclusion Criteria:

* Major cognitive deficits or psychiatric problems hampering a self-reported evaluation.
* Not speaking and reading the language of the participating country.
* Having received any CML treatment prior to therapy with imatinib or dasatinib for more than three months.

Primary outcomes:
measure: Severity of the impact of therapy on daily life in patients with CP-CML being treated with first line therapy with dasatinib and those receiving first line therapy with imatinib.
timeFrame: 24 months.
Secondary outcomes:
measure: Differences in Patient-reported outcomes between imatinib- and dasatinib- treated CP- CML patients in the following QoL domains: Fatigue, Physical, Social and Role Functioning and Impact on worry and mood and Symptom burden.
timeFrame: 24 months.
measure: Proportion of patients considered as low, medium and high adheres by type of therapy.
timeFrame: 24 months.
measure: Relationship between patient's perception of disease-/treatment-related information received , QoL profile and adherence to therapy.
timeFrame: 24 months.
measure: Degree of agreement in the assessment of symptom severity, for a set of core CML treatment related symptoms , between patients and their treating physicians.
timeFrame: 24 months.
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: Department of Hematology and Oncology, Hôpital Mignot, Université Versailles Saint-Quentin-en-Yvelines
city: Mannheim
country: Germany
facility: Universität Heidelberg - III. Medizinische Klinik - Universitätsmedizin Mannheim
city: Mannhein
country: Germany
facility: Universitat Heidelberg
city: Alessandria
country: Italy
facility: S. C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
city: Ancona
country: Italy
facility: Clinica di Ematologia - Azienda Ospedaliera Regionale di Torrette
city: Bari
country: Italy
facility: U.O. Ematologia con trapianto - Azienda Ospedaliero-Universitaria Policlinico di Bari
city: Bologna
country: Italy
facility: Istituto di Ematologia "L. e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
city: Brescia
country: Italy
facility: USD - Centro Trapianti Midollo Osseo Adulti - Cattedra di Ematologia - Azienda Spedali Civili - Brescia
city: Brindisi
country: Italy
facility: U.O. Ematologia Brindisi- Ospedale A. Perrino ASL BR
city: Cagliari
country: Italy
facility: CTMO-Ematologia-Ospedale "Binaghi"
city: Cagliary
country: Italy
facility: U.O. Ematologia CTMO "Businco"
city: Catania
country: Italy
facility: Divisione clinicizzata di Ematologia - Dipartimento di Scienze Mediche - Osp. Ferrarotto
city: Ferrara
country: Italy
facility: Azienda Ospedaliera - Arcispedale S. Anna Sezione di Ematologia e Fisiopatologia delle Emostasi
city: Firenze
country: Italy
facility: Divisione di Ematologia - Policlinico Careggi
city: Genova
country: Italy
facility: Clinica Ematologica - Dipartimento di Medicina Interna - IRCCS San Martino - IST
city: Messina
country: Italy
facility: Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
city: Messina
country: Italy
facility: Divisione Ematologia - Dipartimento di Medicina Interna -Policlinico Universitario di Messina
city: Mestre - Venezia
country: Italy
facility: U.O. Ematologia - Azienda USLL12 Veneziana - Ospedale dell'Angelo e Ospedale civile S. Giovanni e Paolo
city: Milano
country: Italy
facility: U.O. Ematologia 1 - Centro Trapianti di Midollo - Ospedale Maggiore Milano
city: Napoli
country: Italy
facility: Dipartimento di Med. Clinica e Sperimentale- Area di Ematologia - Facoltà di Medicina e Chirurgia - Università degli Studi di Napoli "Federico II" -
city: Napoli
country: Italy
facility: U.O. Ematologia - Ospedale S. Gennaro
city: Napoli
country: Italy
facility: XIX Divisione di Ematologia con trapianto - A.O.R.N. "A. Cardarelli"
city: Novara
country: Italy
facility: Divisione di Ematologia - Dip. Di Medicina Clinica e Sperimentale & BRMA - Università Piemonte Orientale "Amedeo Avogato"
city: Orbassano
country: Italy
facility: Dipartimento di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga
city: Padova
country: Italy
facility: Ematologia ed Immunologia Clinica - Università degli studi di Padova
city: Palermo
country: Italy
facility: Divisione di Ematologia con trapianto di midollo - A.O.U. Policlinico "Paolo Giaccone"
city: Palermo
country: Italy
facility: U.O.C. Ematologia - A.O. Ospedali Riuniti "Villa Sofia-Cervello"
city: Parma
country: Italy
facility: Ematologia e CTMO - A.O.U. Università degli Studi di Parma
city: Piacenza
country: Italy
facility: Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
city: Pisa
country: Italy
facility: U.O. Ematologia - A.O.U. Pisana
city: Potenza
country: Italy
facility: U.O. Ematologia - A.O. San Carlo
city: Reggio Calabria
country: Italy
facility: Divisione di Ematologia - A.O. Ospedali Riuniti di Reggio Calabria "Bianchi-Melacrino-Morelli"
city: Rimini
country: Italy
facility: Rimini Ospedale "Infermi"
city: Rionero in Vulture
country: Italy
facility: Department of Onco-Hematology - IRCCS; Centro di Riferimento Oncologico della Basilicata
city: Roma
country: Italy
facility: Clinica di Ematologia - Policlinico Umberto I- Università degli Studi "Sapienza"
city: Roma
country: Italy
facility: Divisione di Ematologia - Ospedale S.Eugenio
city: Roma
country: Italy
facility: Ematologia - A.O. Sant'Andrea
city: Roma
country: Italy
facility: Ematologia Policlinico - Università degli Studi di Roma Tor Vergata (PTV)
city: Roma
country: Italy
facility: U.O. di Ematologia - Ente Ospedaliero San Giovanni Addolorata
city: Roma
country: Italy
facility: U.O.C. Ematologia e Trapianto cellule staminali - Pad Cesalpino- A.O. San Camillo Forlanini
city: San Giovanni Rotondo
country: Italy
facility: U.O. di Ematologia - Casa Sollievo della Sofferenza
city: Sassari
country: Italy
facility: Ematologia - AOU Sassari
city: Taranto
country: Italy
facility: U.O.C. Ematologia - A.O. SS Annunziata - P.O.S.G. Moscati
city: Terni
country: Italy
facility: S.C. di Oncoematologia - A.O. "S. Maria"
city: Torino
country: Italy
facility: S.C.D.O. Ematologia II - A.O.U.S. San Giovanni Battista di Torino (Molinette)
city: Udine
country: Italy
facility: Clinica Ematologica ed Unità di Terapie Cellulari Carlo Melzi - A.O. Universitaria
city: Vercelli
country: Italy
facility: Onco-Ematologia - Ospedale S. Andrea- Vercelli
city: Verona
country: Italy
facility: U.O di Ematologia d. U. - Azienda Ospedaliera Universitaria Integrata Verona
city: Madrid
country: Spain
facility: Department of Hematology, Hospital Universitario de la Princesa
Study officials:
affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto
name: Fabio Efficace, PhD
role: STUDY_CHAIR
affiliation: University of Bologna
name: Gianantonio Rosti, Dr.
role: STUDY_DIRECTOR
References: