Clinical Trial: Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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-

Brief Summary:

Trial Design:

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.

Disease:

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.

Calendar:

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).


Detailed Summary:

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
Sponsor: Fundación General de la Universidad de Salamanca

Current Primary Outcome:

  • Period until the progression of myelodysplastic syndrome [ Time Frame: 6 years (study treatment and follow up) ]
    To assess if treatment with Revlimid (Lenalidomide) extends the period until the progression to MDS of(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 MDS associated with the loss of 5q without transfusion dependent anemia, which is the therapeutic abstention and monitoring until its progression.
  • Safety [ Time Frame: 6 years (study treatment and follow up) ]
    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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Erythroid response [ Time Frame: 6 years (study treatment and follow up) ]
    Erythroid response according to the Criteria of the MDS International Work Team.
  • Duration of the red blood cells transfusion independency [ Time Frame: 6 years (study treatment and follow up) ]
    Red blood cells transfusion independency,defined as the number of days elapsed between the randomization and the first transfusion after this period free of transfusions.
  • Change of the hemoglobin concentration (Hb) in relation to baseline levels [ Time Frame: 6 years (study treatment and follow up) ]
    Change of the hemoglobin concentration (Hb) in relation to baseline levels of patients who show erythroid response.
  • Variation in platelets and neutrophils absolute count in relation to baseline levels [ Time Frame: 6 years (study treatment and follow up) ]
  • Cytogenetic response [ Time Frame: 6 years (study treatment and follow up) ]
    Cytogenetic response according to the Criteria of the MDS International Work Team.
  • Bone marrow response [ Time Frame: 6 years (study treatment and follow up) ]
    Bone marrow response according to the Criteria of the MDS International Work Team.
  • Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia. [ Time Frame: 6 years (study treatment and follow up) ]
  • Time from diagnose to transfusion independence. [ Time Frame: 6 years (study treatment and follow up) ]


Original Secondary Outcome: Same as current

Information By: Fundación General de la Universidad de Salamanca

Dates:
Date Received: November 17, 2010
Date Started: January 2010
Date Completion: January 2022
Last Updated: April 18, 2016
Last Verified: April 2016