Clinical trial NCT02085798: Health Outcomes of Recently Diagnosed Myelodysplastic Syndrome (MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Depending on Treatment Strategy (Wait and See, Support, Active Treatment)
Official title: Post-authorization, Observational Study to Assess the Evolution in the Normal Clinical Practise of Patients With Recent Diagnosis of Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML), Depending on the Time of Active Treatment Initiated
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myelodysplastic Syndrome
Leukemia, Myelomonocytic, Chronic
Keywords: Leukemia, Myelomonocytic, Chronic, myelodysplastic syndrome, Prospective, Treatment strategy, epidemiologic data
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-03-13
Enrollment: 503
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients recently diagnosed (within the last 3 months prior to entering the study) of SMD or CMML, naïve to active treatment.

Brief summary: Post-authorisation observational study to assess the evolution in normal clinical practice of patients recently diagnosed with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukaemia (CMML), depending on the moment when active treatment is initiated. Subjects will be recruited from approximately 50 haematology sites in Spain.

Detailed description: Observational, prospective, post-authorisation multicentre study.

The study will include patients with a recent diagnosis (\< 3 months) of MDS or CMML, receiving immediate active/support treatment or for whom an observation approach ("wait and see") is initially adopted, as per normal clinical practice in each participating site.

The minimum follow-up period of a participant patient will be 36 months from recruitment, until survival can be documented, differentiating between

1. Patients starting immediate active treatment: data will be collected every 3 months or every time an event arises during the active treatment phase. After the final dose of the initial treatment therapy, data collection will take place every 6 months during the post-treatment follow-up phase, regardless of the number of times the patient attends medical appointments, up to a minimum of 36 months' follow-up from the start of active treatment.
2. Patients for whom initial treatment strategy is support treatment or observation: a minimum follow-up period of 36 months will be established from the date of inclusion in the study, with data collection every 6 months or whenever an event occurs, regardless of the number of times the patient attends a medical appointment. The need for treatment for MDS (o CMML, where applicable) during this period will be considered an event, after which data will be collected every 3 months or each time an event occurs during the entire active treatment phase. After the final dose of the initial treatment therapy, data collection will take place every 6 months during the post-treatment follow-up phase, regardless of the number of times the patient attends medical appointments, up to a minimum of 36 months' follow-up from the start of active treatment.

Patients will be included consecutively, without the treatment prescription decisions affecting the decision to include the patient in the study. Indeed, in order to ensure the presence of patients with MDS of different prognoses and of patients with CMML, inclusion will be stratified into the following three cohorts, each of which will include patients receiving immediate treatment and those initially opting for observation/support:

* Group 1: Patients with low or intermediate-1 risk MDS as per the International Prognostic Scoring System (IPSS) 1.
* Group 2: Patients with intermediate-2 or high risk MDS as per IPSS.
* Group 3: Patients with any type of CMML as per the prognosis index CMML Prognostic Scoring System (CPSS) 2.

A total of 600 patients are expected to be recruited from 50 sites.

Primary objective:

To assess clinical evolution from the time of diagnosis in patients with MDS or CMML, within normal clinical practice.

The study will assess event free survival (EFS) depending on the therapeutic strategy initially adopted by the investigator after a diagnosis of MDS or CMML under normal clinical practice conditions.

EFS is defined as the period of time elapsed between diagnosis of the condition (MDS or CMML) and the appearance of one of the following events:

* Progression of the disease, or
* All-cause death, or
* Appearance of a clinically significant condition requiring a change in initial therapeutic strategy, or
* Appearance of an adverse event\* requiring treatment to be suspended. \*This applies to all patients included in the study, under active or support treatment.

Secondary objectives:

1. To describe the demographic, clinical (including MDS or CMML classification as per WHO 2008 (5, 19)), and analytical characteristics of patients recently diagnosed with MDS or CMML. Clinical characteristics include a health assessment as per the CIRS-G scale (Cumulative Illness Rating Scale for Geriatrics), the comorbidity rating for SMD (MDS-CI) by Della Porta and Malcovatti, 20 or other scale used across all participating sites in normal clinical practice, and the performance status of the patient as per ECOG scale.
2. To describe the therapeutic strategies initially applied for patients with MDS or CMML, based on clinical characteristics (specific cytogenetic alterations, adverse events, etc.), age, health status (CIRS-G scale), ECOG and IPSS (IPSS-R) or CPSS, in addition to the reasons for adopting different initial therapeutic strategies.
3. To analyse the response of MDS/CMML to treatment based on the IWG ( International Working Group) response criteria in myelodysplasia, modified in 2006.
4. To describe patient evolution based on time-dependent response parameters.

   * Time to Progression of the disease (TTP) as per the IWG response criteria modified in 2006.
   * Evolution to acute myeloblastic leukaemia (AML) (median time until transformation into AML).
   * To analyse progression free survival (PFS) from inclusion in the study until documented progression of MDS or CMML or death during follow-up.
   * Overall survival (OS) measured from the date of diagnosis of the disease until date of all-cause death, where applicable.
   * Assessment of overall response rate of dependence on red blood cell and platelet transfusions.
5. To document the tolerance profile (safety) of the treatment administered under normal clinical practice conditions.
6. To describe the use of healthcare resources relating to the initial therapeutic strategy for MDS or CMML in normal clinical practice, which can be financially measured, and to explore the possible differences both between the treat/do not treat option and the different therapeutic regimens administered.
7. To describe clinically significant events requiring a change in initial therapeutic strategy (counting for EFS, the primary objective of the study).

Eligibility criteria: Inclusion Criteria:

-1. Male or female subjects, aged 18 years or older. 2. Subjects with documented diagose of MDS or CMML within the last 3 months prior to entering the study and naive to treatment.

3. Signed informed consent.

Exclusion Criteria:

* 1. Subjects participating in an interventional clinical trial 2. Subjects who do not agree to participate.

Primary outcomes:
measure: Event Free Survival
timeFrame: Up to a minimum of 36 months' follow-up from the start of active treatment
Secondary outcomes:
measure: Health Assesment/performance Status
timeFrame: Approximately 3 years
measure: Response to active treatment
timeFrame: Up to end of treatment for each patient
measure: Patient evolution based on time-dependent response parameters
timeFrame: Approximately 3 years
measure: Adverse Events
timeFrame: Approximately 3 years
measure: Patient Description
timeFrame: Baseline
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital Universitario Txagorritxu
state: Alava
city: Alzira
country: Spain
facility: Hospital Universitario La Ribera
state: Alicante
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
state: Barcelona
city: Alcázar de San Juan
country: Spain
facility: Complejo Hospitalrio La Mancha Centro
state: Ciudad Real
city: Algeciras
country: Spain
facility: Hospital Punta de Europa
state: Cádiz
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
state: Guipuzcoa
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Getafe
country: Spain
facility: Hospital Universitario Getafe
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Hospital De Antequera
country: Spain
facility: Hospital de Antequera
state: Málaga
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Talavera de la Reina
country: Spain
facility: Hospital Nuestra Señora del Prado
state: Toledo
city: Almeria
country: Spain
facility: Complejo Hospitalario Torrecárdenas
city: Barcelona
country: Spain
facility: Parc de Salut Mar- Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Duran Reynals
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Girona
country: Spain
facility: Hospital Universitari de Girona Josep Trueta
city: Ibiza
country: Spain
facility: Hospital Can Misses
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
city: Las Palmas de Gran Canaria
country: Spain
facility: CHU-Insular
city: León
country: Spain
facility: Hospital de León
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Fundación Jimenez Díaz
city: Murcia
country: Spain
facility: Hospital General Universitario Santa Lucía
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Ourense
country: Spain
facility: Complejo Universitario Hospitalario de Ourense
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
city: Pontevedra
country: Spain
facility: Complejo Hospitalrio Universitario de Pontevedra
city: Salamanca
country: Spain
facility: Hospital Universitario Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Hospital de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Soria
country: Spain
facility: Hospital Santa Bárbara
city: Valencia
country: Spain
facility: Hospital Clínico Universitario Valencia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Celgene Spain
name: Montserrat Rafel, RML Advocacy
role: STUDY_DIRECTOR
affiliation: Hospital Clínico Virgen de la Victoria, Málaga, Spain
name: Regina Garcia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Vall d'Hebron, Barcelona, Spain
name: David Valcárcel, MD
role: PRINCIPAL_INVESTIGATOR
References: