This clinical trial is a phase III multicenter, randomized, double blind and controlled with placebo trial and with two arms designed to assess the efficiency and toxicity of the scheme Lenalidomide versus observation in a series of 60 patients with low risk myelodysplastic syndrome associated to 5q deletion with anemia (Hb≤12g/dL) but without the need of transfusion. Patients are randomized in the study in a 2:1 ratio. They will receive treatment for 104 weeks until progression of the disease, which implies that the patient suffering from anemia due to myelodysplastic syndrome requires transfusion of at least 2 UCH/56 days (2 months) with a minimum follow up of 112 days (4 months), or unacceptable toxicity.
Low risk myelodysplastic syndrome associated to the loss of 5q without transfusion requirements.
Total number of patients:
In total 60 patients will be included, 40 assigned to the treatment branch and 20 to the placebo branch.
First patient first visit: February 2010, and Last patient last visit expected in February 2016. (Recruitment was initially expected to take place over a period of 24 months and was expected to be finished in February 2012, but due to low rate of recruitment it was extended until the population sample is included in the trial).
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Multicenter, Randomized, Double-blind, Phase III Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 IPSS) With Alteration in 5q- and Anemia Without the Need of Transfusion.|
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2022|
|Estimated Primary Completion Date:||September 2021 (Final data collection date for primary outcome measure)|
Experimental treatment branch with Lenalidomide 5 mg/day (oral use)
Treatment with Revlimid (lenalidomide), oral use, 5 mg daily during study treatment (104 weeks).
Other Name: Revlimid 5 mg
Placebo Comparator: placebo
Placebo branch (oral use)
Placebo, oral use, daily during study treatment (104 weeks)
General summary of myelodysplastic syndrome with alteration in 5q. Myelodysplastic syndromes (MDS) are a very heterogenic group of diseases characterized by the presence of morphologic features of dyshemopoiesis in bone marrow (BM) and in peripheral blood (PB), which is translated into an inefficient hematopoiesis. This will lead to the concomitant development of peripheral cytopenias which will be the cause of complications in these patients and, in most cases, the cause of death. In addition, these patients have an increased risk of developing acute leukemia, and this risk increases with the progression of the disease.MDS represents an incurable disease with standard treatments with a quite variable survival mean ranging from 3 months to 15 years depending on the number of blasts, the number of cytopenias and the type of cytogenetic disorders2. The sole curative treatment of the MDS is the allogenic transplant of hematopoietic progenitors but this option is only available for a 5% of the patients with MDS.
Lenalidomide, initially known as CC-5013, is an analogue of the immunomodulator Drug Thalidomide (Thalidomid®; Pharmion Corp., Boulder, CO, USA), which was the first drug with anti-angiogenic and immunomodulator properties investigated in MDS. Lenalidomide has, as well as thalidomide, a broad array of potential activities against dysplastic cells, not fully known, among which we find immunomodulator and non-immunomodulator properties (anti-angiogenic effect, anti-proliferative and pro-apoptotic). The greater advantage of Lenalidomide in comparison with thalidomide is that the former is between 50 and 2000 times stronger tan thalidomide in what respects to its immunomodulator effects. And moreover, the toxic profile of Lenalidomide seems lower than that of its analogue; Thalidomide.
There is no treatment indication on the present times for patients with low risk MDS associated to the loss of 5q without transfusion dependent anemia. The results with Lenalidomide are highly promising for patients with low risk MDS associated to the loss of 5q when (it has so been tested) there is red blood cells transfusion dependent anemia. In this sense, the proposal consists on being able to state that treatment with Lenalidomide can be efficient from diagnose preventing CH transfusions with an acceptable toxicity.
In this sense, the present study has the intention to treat early patients with low-risk MDS associated to the loss of 5q with a view to prevent CH transfusion. Therefore, we could extend in these patients the time until CH transfusion and even assess the possibility of eradicating the disease at a cytogenetic/morphologic level. In the present trial and given the characteristics of the patients, we have chosen the option of supplying Lenalidomide at a dose of 5mg/day. The option of considering a lower dose to the one currently considered as "standard" (10mg/day) is to reduce toxicity, mainly hematologic, in patients who do not receive treatment normally. A dose with lower toxicity has been chosen which has revealed itself efficient.
Main efficiency objective:
•To assess if treatment with Revlimid (Lenalidomide) extends the period until the progression to myelodysplastic syndrome del(5q) considered as transfusion independent, documented verification that the patient suffering from anemia due to MDS requires transfusion of at least 2 UCH/56 days (2 months) with a minimum follow up of 112 days (4 months). Revlimid will be compared to the current standard treatment for patients with low risk myelodysplastic syndrome associated with the loss of 5qwithout transfusion dependent anemia, which is the therapeutic abstention and monitoring until its progression.
Secondary efficiency objectives:
Main safety objective:
Safety (type, frequency and severity [Criteria of normal terminology of adverse reactions of the National Cancer Institute (NCI CTCAE) version 3.0] of adverse reactions (AR)and list of the AR with Lenalidomide.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01243476
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01243476
|Hospital de Cabueñes||Terminated|
|Gijón, Asturias, Spain, 33394|
|Hospital Central de Asturias||Recruiting|
|Oviedo, Asturias, Spain, 33006|
|Contact: Teresa Bernal del Castillo, MD 0034 985 108 000 ext 39179 email@example.com|
|Principal Investigator: Teresa Bernal del Castillo, MD|
|Hospital Universitari Germans Trias i Pujol (ICO Badalona)||Recruiting|
|Badalona, Barcelona, Spain, 08916|
|Contact: Blanca Xicoy Cirici, MD 0034 93 497 89 24 firstname.lastname@example.org|
|Principal Investigator: Blanca Xicoy Cirici, MD|
|Hospital Son Llàtzer||Recruiting|
|Palma de Mallorca, Islas Baleares, Spain, 07198|
|Contact: Joan Bargay Lleonart, MD 0034 871 20 21 38 email@example.com|
|Principal Investigator: Joan Bargay Lleonart, MD|
|Hospital de Cruces||Recruiting|
|Barakaldo, Vizcaya, Spain, 48930|
|Contact: Beatriz Arrizabalaga Amuchastegui, MD 0034 946 00 60 89 BEATRIZ.ARRIZABALAGAAMUCHASTEG@osakidetza.net|
|Principal Investigator: Beatriz Arrizabalaga Amuchastegui, MD|
|Hospital Clínic i Provincial||Recruiting|
|Barcelona, Spain, 08036|
|Contact: Benet Nomdedeu Tobella, MD 0034 93 227 54 00 ext 2805 firstname.lastname@example.org|
|Principal Investigator: Benet Nomdedeu Tobella, MD|
|Hospital Universitario Reina Sofía||Recruiting|
|Córdoba, Spain, 14004|
|Contact: Joaquín Sánchez García, MD 0034 957 010 176 email@example.com|
|Principal Investigator: Joaquín Sánchez García, MD|
|Hospital Infanta Leonor||Recruiting|
|Madrid, Spain, 28031|
|Contact: José Angel Hernandez Rivas, MD 0034 911918507 firstname.lastname@example.org|
|Principal Investigator: José Angel Hernandez Rivas, MD|
|Hospital Clínico San Carlos||Terminated|
|Madrid, Spain, 28040|
|Hospital Universitario La Paz||Terminated|
|Madrid, Spain, 28046|
|Hospital General Universitario José Maria Morales Meseguer||Recruiting|
|Murcia, Spain, 30008|
|Contact: Maria Luz Amigo Lozano, MD 0034 968 36 09 00 email@example.com|
|Principal Investigator: Mª Luz Amigo Lozano, MD|
|Hospital Clínico Universitario de Salamanca||Recruiting|
|Salamanca, Spain, 37007|
|Contact: María Díez Campelo, MD 0034 923 29 13 16 firstname.lastname@example.org|
|Principal Investigator: María Díez Campelo, MD|
|Hospital Universitario Virgen del Rocío||Terminated|
|Sevilla, Spain, 41013|
|Hospital Universitario La Fe||Recruiting|
|Valencia, Spain, 46009|
|Contact: Guillermo Sanz Santillana, MD 0034 96 386 27 09 email@example.com|
|Principal Investigator: Guillermo Sanz Santillana, MD|
|Study Chair:||Consuelo del Cañizo, MD||Hospital Clínico Universitario de Salamanca|
|Study Chair:||María Díez Campelo, MD||Hospital Clínico Universitario de Salamanca|