Clinical Trials /

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

NCT01243476

Description:

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).

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: SINTRA-REV
  • SECONDARY ID: 2009-013619-36
  • NCT ID: NCT01243476

Conditions

  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
LenalidomideRevlimid 5 mglenalidomide

Purpose

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 Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
lenalidomideExperimentalExperimental treatment branch with Lenalidomide 5 mg/day (oral use)
  • Lenalidomide
placeboPlacebo ComparatorPlacebo branch (oral use)

    Eligibility Criteria

            Inclusion Criteria:
    
              1. - The patient must, in the investigator's opinion, be able to comply with all the
                 clinical trial requirements.
    
              2. - The patient must voluntarily sign the informed consent form before undergoing any
                 test of the trial that is not part of the normal patient care, and patient must be
                 aware that he/she can withdraw from the trial at any time, without it ever affecting
                 their future healthcare.
    
              3. - Age > 18 years.
    
              4. - The patient must be diagnosed with low risk MDS (low and intermediate-1 IPSS)
                 associated with 5q deletion, either as an isolated abnormality or accompanied by other
                 additional cytogenetic abnormalities.
    
              5. - MDS Del(5q) with transfusion-independent anaemia (Hb ≤ 12 g/dL), and documented
                 confirmation that no packed red blood cells transfusion due to the patient's
                 underlying condition (MDS) has been received.
    
              6. - The patient must have an ECOG performance status of ≤ 2.
    
              7. - The patient must be able to comply with the scheduled study visits.
    
              8. - Female patient with childbearing potential must*:
    
                   -  Understands the teratogenic risk of the study drug.
    
                   -  Commits herself to use two forms of effective birth control continuously, and is
                      able to use them correctly, for the 4 weeks prior to starting treatment with the
                      study drug, as well as during treatment with the study drug (including periods of
                      dose interruption), and for up to 4 weeks after finishing treatment with the
                      study drug, even if amenorrhoeic. This always applies, except in women who commit
                      to continued complete sexual abstinence, as confirmed on a monthly basis.
    
                   -  The patient must understand that even if she is amenorrhoeic she must follow all
                      the advice on effective contraception.
    
                   -  The patient must understand the possible consequences of pregnancy and the need
                      to attend a healthcare service urgently in case there is a risk of pregnancy.
    
                   -  Agree to undergo a pregnancy test with a minimum sensitivity of 25 mIU/mL, under
                      medical supervision, on the day of the study visit or during the 3 days prior to
                      this visit, after using effective birth control for at least 4 weeks. This
                      requirement also applies to women with childbearing potential who practice
                      complete and continued sexual abstinence. The test must confirm that the patient
                      is not pregnant at the time the treatment is initiated.
    
                   -  Agree to undergo a pregnancy test, under medical supervision, weekly for he first
                      28 days of treatment, and subsequently every 4 weeks, including a pregnancy test
                      4 weeks after finishing the study treatment, except in case of confirmed tubal
                      ligation. This pregnancy test will be performed on the day of the study visit or
                      during the 3 days prior to it. This requirement also applies to women with
                      childbearing potential who practice complete and continued sexual abstinence.
    
              9. - All male patients must:
    
                   -  Commit himself to the use of condoms throughout all the treatment with the study
                      drug, including all periods of dose interruption, and up to one week after
                      finishing the treatment if their partner is a woman with childbearing potential
                      and does not use birth control methods.
    
                   -  Commit himself to not donate semen during treatment with the study drug and up to
                      one week after finishing the treatment.
    
             10. - All patients must:
    
                   -  Refrain from donating blood while receiving treatment with the study drug and
                      during the week following the end of the treatment.
    
                   -  Refrain from sharing the study drug with others, and return all unused study drug
                      to the investigator or pharmacist.
    
            Exclusion Criteria:
    
              1. - Any organic disease or psychiatric disorder which makes it impossible for the
                 patient to sign or understand the informed consent.
    
              2. - Having received any treatment for MDS.
    
              3. - Del(5q) MDS with transfusion-dependent anaemia, and documented confirmation that the
                 patient has received any pRBC transfusion due to the underlying condition (MDS).
    
              4. - Pregnant or breast-feeding women.
    
              5. - Any of the following laboratory abnormalities:
    
                   -  Absolute neutrophil count < 500/mm3
    
                   -  Platelet count < 25,000/mm3
    
                   -  Serum GOT or GPT > 3 times the upper limit of normal values.
    
                   -  Total serum bilirubin > 2 times the upper limit of normal values.
    
              6. - Previous history of other malignancies other than MDS (except for basal cell or
                 squamous cell skin carcinoma, or carcinoma in situ of the cervix or breast), unless
                 the patient has been free of disease for more than 5 years.
    
              7. - Known hypersensitivity to or a 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 investigational agent in the 30 days prior to
                 inclusion.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Period until the progression of myelodysplastic syndrome
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    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.

    Secondary Outcome Measures

    Measure:Erythroid response
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:Erythroid response according to the Criteria of the MDS International Work Team.
    Measure:Duration of the red blood cells transfusion independency
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description: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.
    Measure:Change of the hemoglobin concentration (Hb) in relation to baseline levels
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:Change of the hemoglobin concentration (Hb) in relation to baseline levels of patients who show erythroid response.
    Measure:Variation in platelets and neutrophils absolute count in relation to baseline levels
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:
    Measure:Cytogenetic response
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:Cytogenetic response according to the Criteria of the MDS International Work Team.
    Measure:Bone marrow response
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:Bone marrow response according to the Criteria of the MDS International Work Team.
    Measure:Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia.
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:
    Measure:Time from diagnose to transfusion independence.
    Time Frame:6 years (study treatment and follow up)
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Fundación General de la Universidad de Salamanca

    Trial Keywords

    • myelodysplastic syndrome
    • 5q deletion
    • anemia
    • lenalidomide
    • red blood cells transfusion

    Last Updated

    April 18, 2016