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Completed

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

ClinicalTrials.gov ID NCT01243476
Sponsor Fundación General de la Universidad de Salamanca
Information provided by Fundación General de la Universidad de Salamanca (Responsible Party)
Last Update Posted 2023-02-15
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Study Overview

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).

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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.

Four of the sites of this Clinical Trial are member of the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) which is partially co-funded by the European Union within the framework of the Third Health Programme. "ERN-2016 - Framework Partnership Agreement 2017-2021." FPA 739541".

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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.
Conditions
Myelodysplastic Syndrome
Intervention / Treatment
  • Drug: Lenalidomide
  • Other: Placebo
  • Drug: Lenalidomide
  • Other: Placebo
Other Study ID Numbers
  • SINTRA-REV
  • 2009-013619-36 ( EudraCT Number )
    2009-013619-36 ( EudraCT Number )
Study Start
2010-01
Primary Completion (Actual)
2022-06-06
Study Completion (Actual)
2022-06-06
Enrollment (Actual)
61
Study Type
Interventional
Phase
Phase 3

Contacts and Locations

This section provides contact details for people who can answer questions about joining this study, and information on where this study is taking place.

To learn more, please see the Contacts and Locations section in How to Read a Study Record(https://clinicaltrials.gov/study-basics/how-to-read-study-record#contacts-and-locations).

This study has 25 locations
France
Paris, France, 75010

Hôspital St. Louis
Bajo Rin Locations
Strasbourg, Bajo Rin, France, 67091

Hôpitaux Universitaires de Strasbourg
Gard Locations
Nîmes, Gard, France, 30900

Centre Hospitalier Universitaire de Nîmes
Loiret Locations
Orléans, Loiret, France, 45100

Centre Hospitalier Régional d'Orléans
Maine Y Loira Locations
Angers, Maine Y Loira, France, 49100

Centre Hospitalier Universitaire d'Angers
Meurthe Y Mosel Locations
Nancy, Meurthe Y Mosel, France, 54500

Centre Hospitalier Universitaire Brabois
Vaucluse Locations
Avignon, Vaucluse, France, 84000

Centre Hospitalier d'Avignon
Germany
Dresden, Germany, 01307

Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden
Duesseldorf, Germany, 40479

Marien Hospital Duesseldorf
München, Germany, 81675

Klinikum rechts der Isar der Technischen Universität München
Spain
Barcelona, Spain, 08036

Hospital Clínic i Provincial
Córdoba, Spain, 14004

Hospital Universitario Reina Sofía
Gerona, Spain, 17007

Instituto Catalán de Oncología de Gerona
Madrid, Spain, 28031

Hospital Infanta Leonor
Madrid, Spain, 28040

Hospital Clínico San Carlos
Madrid, Spain, 28046

Hospital Universitario La Paz
Murcia, Spain, 30008

Hospital General Universitario José Maria Morales Meseguer
Salamanca, Spain, 37007

Hospital Clínico Universitario de Salamanca
Sevilla, Spain, 41013

Hospital Universitario Virgen del Rocío
Valencia, Spain, 46009

Hospital Universitario La Fe
Asturias Locations
Gijón, Asturias, Spain, 33394

Hospital de Cabueñes
Oviedo, Asturias, Spain, 33006

Hospital Central de Asturias
Barcelona Locations
Badalona, Barcelona, Spain, 08916

Hospital Universitari Germans Trias i Pujol (ICO Badalona)
Islas Baleares Locations
Palma de Mallorca, Islas Baleares, Spain, 07198

Hospital Son Llàtzer
Vizcaya Locations
Barakaldo, Vizcaya, Spain, 48930

Hospital de Cruces
Click to view interactive map

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies(https://clinicaltrials.gov/study-basics/learn-about-studies).
Eligibility Criteria
Description

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.
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Ages Eligible for Study
18 Years and older (AdultOlder Adult )
Sexes Eligible for Study
All
Accepts Healthy Volunteers
No

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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Design Details
Primary Purpose : Treatment
Allocation : Randomized
Interventional Model : Parallel Assignment
Masking : Quadruple (ParticipantCare ProviderInvestigatorOutcomes Assessor)

Arms and Interventions

Participant Group/Arm Intervention/Treatment
Participant Group/Arm Experimental: lenalidomide
Experimental treatment branch with Lenalidomide 5 mg/day (oral use)
Intervention/Treatment Drug: Lenalidomide
  • Treatment with Revlimid (lenalidomide), oral use, 5 mg daily during study treatment (104 weeks).

  • Other Names:
    • Revlimid 5 mg
Participant Group/Arm Placebo Comparator: placebo
Placebo branch (oral use)
Intervention/Treatment Other: Placebo
  • Placebo, oral use, daily during study treatment (104 weeks)

Primary Outcome Measures
Outcome Measure Measure Description Time Frame
Period until the progression of myelodysplastic syndromeTo 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)
Secondary Outcome Measures
Outcome Measure Measure Description Time Frame
Erythroid responseErythroid response according to the Criteria of the MDS International Work Team.6 years (study treatment and follow up)
Duration of the red blood cells transfusion independencyRed blood cells transfusion independency,defined as the number of days elapsed between the randomization and the first transfusion after this period free of transfusions.6 years (study treatment and follow up)
Change of the hemoglobin concentration (Hb) in relation to baseline levelsChange of the hemoglobin concentration (Hb) in relation to baseline levels of patients who show erythroid response.6 years (study treatment and follow up)
Variation in platelets and neutrophils absolute count in relation to baseline levelsVariation in platelets and neutrophils absolute count in relation to baseline levels6 years (study treatment and follow up)
Cytogenetic responseCytogenetic response according to the Criteria of the MDS International Work Team.6 years (study treatment and follow up)
Bone marrow responseBone marrow response according to the Criteria of the MDS International Work Team.6 years (study treatment and follow up)
Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia.Global survival, Event Free Survival and Rate of Transformation to Acute Leukemia6 years (study treatment and follow up)
Time from diagnose to transfusion independence.Time from diagnose to transfusion independence6 years (study treatment and follow up)
Safety( type, frequency and severity of adverse events and relationship to lenalidomideSafety (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.6 years (study treatment and follow up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.
Sponsor
Fundación General de la Universidad de Salamanca
Collaborators
  • Celgene Corporation
Investigators
  • Study Chair:Consuelo del Cañizo, MD,Hospital Clínico Universitario de Salamanca
  • Study Chair:María Díez Campelo, MD,Hospital Clínico Universitario de Salamanca

Publications

General

These publications are provided voluntarily by the person who enters information about the study and may be about anything related to the study.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates
First Submitted
2010-11-17
First Submitted that Met QC Criteria
2010-11-17
First Posted (Estimated)
2010-11-18
Study Record Updates
Last Update Submitted that met QC Criteria
2023-02-14
Last Update Posted
2023-02-15
Last Verified
2023-01

More Information

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Keywords Provided by Fundación General de la Universidad de Salamanca
Additional Relevant MeSH Terms