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.
18 Years
N/A
Both
Myelodysplastic Syndrome
Trial Information
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
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:
- 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
transfusions).
- 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.
Inclusion Criteria:
1. Patient must be capable of meeting all requirements of the clinical trial.
2. Patient will have to freely sign the informed consent before undergoing any test of
the trial which does not form part of the normal care of patients
3. Age > 18 years.
4. Patient will have to have a diagnose of low risk myelodysplastic syndrome (MDS)(low
and intermediate-1 IPSS)associated to the loss of 5q, either as isolated abnormality
or accompanied by other additional cytogenetic abnormalities.
5. MDS 5q- with anemia (Hb ≤ 12 g/dL) transfusion independent, and documented
confirmation of not having received any transfusion of packed red blood cells due to
his/her baseline disease (MDS).
6. Patient will have a general state measured according to the ECOG scale ≤ 2
7. Patient should be capable of meeting all scheduled visits of the study.
8. All women patient with childbearing potential will have to:
- Understand the teratogenic risk of the study drug
- Commit herself to use an effective contraceptive method on a continuous basis
during the 4 weeks prior to the beginning of the treatment with the drug under
study (including dose interruption periods) and until 4 weeks after the end of
the treatment with drug under study.
- Understand that, even if she suffers amenorrhea, she will have to follow all
warnings in relation to an effective contraception.
- Understand the potential consequences of pregnancy and the need to attend a
healthcare attention service urgently in the event of pregnancy risk.
- Access to the development of a pregnancy tests with a minimum sensibility of
25mUI/ml under medical supervision, on the day of the visit of the study or on
the previous 3 days, when she has been using effective contraceptive methods for
at least 4 weeks.
- Access to the performance of a pregnancy test, under medical supervision, each 4
weeks, including a pregnancy test 4 weeks after the end of the treatment of the
study,unless in the case of confirmed tubal ligation.
9. All male patients will have to:
- Commit themselves to use condoms during all the treatment with the drug under
study, including all dose interruption periods and until one week after the end
of the treatment if his partner is a women with childbearing potential and does
not use contraceptive methods.
- Commit themselves not to donate semen during the treatment with the drug under
study and until one week after the end of the treatment.
10. All patients will have to:
- Refrain from donating blood while receiving treatment with the drug under study
and during the week following its end.
- Refrain from share the drug under study with other people and to return all
drugs under study which have not been used to the investigator or pharmacist.
Exclusion Criteria:
1. Organic disease or psychiatric disorder which made possible that the patient did not
sign nor understood the informed consent.
2. Having received any treatment for MDS.
3. MDS 5q- with transfusion dependent anemia, documented confirmation that the patient
has received some CH transfusion due to the baseline disease (MDS).
4. Pregnant women or on lactation period.
5. Any of the following lab abnormalities:
- Absolute count of neutrophils < 500/mm3
- Platelet count < 25000/mm3
- GOT or GPT in serum > 3 times the normal higher threshold
- Total serum bilirubin > 2 times the normal higher threshold
6. Prior history of other malign disease different to MDS (except for carcinoma of
baseline cells or skin squamous, or cervix or breast in situ carcinoma) unless the
patient is free from disease for more than 5 years.
7. Known hypersensibility or history of uncontrollable side effects to Lenalidomide.
8. Major surgery within the 4 weeks prior to the inclusion in the trial.
9. The patient has received any agent under research in the 30 days prior to the
inclusion
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
Period until the progression of myelodysplastic syndrome
Outcome Description:
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.
Outcome Time Frame:
6 years (study treatment and follow up)
Safety Issue:
No
Principal Investigator
Consuelo del Cañizo, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Hospital Clínico Universitario de Salamanca
Authority:
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Study ID:
SINTRA-REV
NCT ID:
NCT01243476
Start Date:
January 2010
Completion Date:
January 2016
Related Keywords:
- Myelodysplastic Syndrome
- myelodysplastic syndrome
- 5q deletion
- anemia
- lenalidomide
- red blood cells transfusion
- Myelodysplastic Syndromes
- Preleukemia
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