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.
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
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:
- Erythroid response according to the Criteria of the myelodysplastic syndrome
International Work Team 2006).
- Duration of the red blood cells transfusion independency (defined as the number of days
elapsed between the randomization and the first transfusion after this period free of
- Change of hemoglobin concentration (Hb) in relation to baseline levels of patients who
show erythroid response.
- Variation in platelets absolute count in relation to baseline levels.
- Variation in neutrophils absolute count in relation to baseline levels.
- Cytogenetic response according to the Criteria of the myelodysplastic syndrome
International Work Team.
- Bone marrow response according to the Criteria of the myelodysplastic syndrome
International Work Team.
- To assess the safety and tolerance of the Lenalidomide scheme, measured according to
the incidence of clinical and laboratory toxicity.
- Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia.
- Time from diagnose to transfusion independence.
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Period until the progression of myelodysplastic syndrome
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.
6 years (study treatment and follow up)
Consuelo del Cañizo, MD
Hospital Clínico Universitario de Salamanca
Spain: Agencia Española de Medicamentos y Productos Sanitarios