Health Outcomes of Recently Diagnosed Myelodysplastic Syndrome (MDS)/Chronic Myelomonocytic Leukemia (CMML) Patients Depending on Treatment Strategy (Wait and See, Support, Active Treatment)

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT02085798

Collaborator

(none)

503

Enrollment

Locations

71.9

Actual Duration (Months)

10.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome Leukemia, Myelomonocytic, Chronic	Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion

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

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.
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:

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.
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.
To analyse the response of MDS/CMML to treatment based on the IWG ( International Working Group) response criteria in myelodysplasia, modified in 2006.
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.

To document the tolerance profile (safety) of the treatment administered under normal clinical practice conditions.
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.
To describe clinically significant events requiring a change in initial therapeutic strategy (counting for EFS, the primary objective of the study).

Study Design

Study Type:

Observational

Actual Enrollment :

503 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Dec 17, 2012

Actual Primary Completion Date :

Aug 31, 2015

Actual Study Completion Date :

Dec 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Low or intermediate-1 risk MDS patients according to IPSS	Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion As described above
Group 2 Intermediate-2 risk MDS patients according to IPSS	Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion As described above
Group 3 Any risk CMML patients according to CPSS	Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion As described above

Arm

Intervention/Treatment

Group 1

Low or intermediate-1 risk MDS patients according to IPSS

Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion

As described above

Group 2

Intermediate-2 risk MDS patients according to IPSS

Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion

As described above

Group 3

Any risk CMML patients according to CPSS

Other: Either Wait and See, or Supportive Treatment, or Active Treatment at physician discretion

As described above

Outcome Measures

Primary Outcome Measures

Event Free Survival [Up to a minimum of 36 months' follow-up from the start of active treatment]
Period of time elapsed between diagnosis of the condition (MDS or CMML) and the appearance of one of an event: Progression of the disease, death (all causes), clinically significant condition requiring a change in initial therapeutic strategy, adverse event requiring treatment discontinuation

Secondary Outcome Measures

Health Assesment/performance Status [Approximately 3 years]
Changes from baseline to end of study as per CIRS-G scale, MDS-CI, ECOG
Response to active treatment [Up to end of treatment for each patient]
Response to active treatment up to progressions
Patient evolution based on time-dependent response parameters [Approximately 3 years]
Time to progression, time to evolution to AML (median time until transformation into AML), Progression Free Survival (from inclusion into the study to documented progression or death), Overall Survival (from diagnosis to death, all causes), Overall rate of dependence on red blood cells and platelet transfusion
Adverse Events [Approximately 3 years]
Safety profile description of treatment under normal clinical practice conditions
Patient Description [Baseline]
Demography, Clinical history of MDS or CMML, Blood test, Relevant comorbidities variables

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Signed informed consent.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Txagorritxu	Vitoria	Alava	Spain	01009
2	Hospital Universitario La Ribera	Alzira	Alicante	Spain	46600
3	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona	Spain	08916
4	Complejo Hospitalrio La Mancha Centro	Alcázar de San Juan	Ciudad Real	Spain	13600
5	Hospital Punta de Europa	Algeciras	Cádiz	Spain	11207
6	Hospital Universitario Donostia	San Sebastián	Guipuzcoa	Spain	20008
7	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid	Spain	28922
8	Hospital Universitario Getafe	Getafe	Madrid	Spain	28905
9	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
10	Hospital de Antequera	Hospital De Antequera	Málaga	Spain	29200
11	Hospital Costa del Sol	Marbella	Málaga	Spain	29603
12	Hospital Nuestra Señora del Prado	Talavera de la Reina	Toledo	Spain	45600
13	Complejo Hospitalario Torrecárdenas	Almeria		Spain	29010
14	Parc de Salut Mar- Hospital del Mar	Barcelona		Spain	08003
15	Hospital de la Santa Creu I Sant Pau	Barcelona		Spain	08025
16	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
17	Hospital Duran Reynals	Barcelona		Spain	08907
18	Hospital Universitario Puerta del Mar	Cádiz		Spain	11009
19	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
20	Hospital Universitari de Girona Josep Trueta	Girona		Spain	17007
21	Hospital Can Misses	Ibiza		Spain	07800
22	Hospital Universitario de Gran Canaria Doctor Negrín	Las Palmas de Gran Canaria		Spain	35010
23	CHU-Insular	Las Palmas de Gran Canaria		Spain	35016
24	Hospital de León	León		Spain	24071
25	Hospital Lucus Augusti	Lugo		Spain	27003
26	Hospital Universitario Infanta Leonor	Madrid		Spain	28031
27	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
28	Hospital Clínico San Carlos	Madrid		Spain	28040
29	Hospital Fundación Jimenez Díaz	Madrid		Spain	28040
30	Hospital General Universitario Santa Lucía	Murcia		Spain	30202
31	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29010
32	Complejo Universitario Hospitalario de Ourense	Ourense		Spain	32005
33	Hospital Universitario Central de Asturias	Oviedo		Spain	33006
34	Hospital Son Llàtzer	Palma de Mallorca		Spain	07198
35	Complejo Hospitalrio Universitario de Pontevedra	Pontevedra		Spain	36002
36	Hospital Universitario Salamanca	Salamanca		Spain	37007
37	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
38	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela		Spain	15706
39	Hospital General de Segovia	Segovia		Spain	40002
40	Hospital de Valme	Sevilla		Spain	41014
41	Hospital Universitario Virgen Macarena	Sevilla		Spain	41071
42	Hospital Santa Bárbara	Soria		Spain	42005
43	Hospital Clínico Universitario Valencia	Valencia		Spain	46010
44	Hospital Arnau de Vilanova	Valencia		Spain	46015
45	Hospital Universitario Doctor Peset	Valencia		Spain	46017
46	Hospital Universitario La Fe	Valencia		Spain	46026
47	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47005
48	Hospital Universitario Río Hortega	Valladolid		Spain	47012
49	Hospital Clínico Universitario Lozano Blesa	Zaragoza		Spain	50009
50	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

Celgene

Investigators

Study Director: Montserrat Rafel, RML Advocacy, Celgene Spain
Principal Investigator: Regina Garcia, MD, Hospital Clínico Virgen de la Victoria, Málaga, Spain
Principal Investigator: David Valcárcel, MD, Hospital Vall d'Hebron, Barcelona, Spain