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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fundación General de la Universidad de Salamanca
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Fundación General de la Universidad de Salamanca
ClinicalTrials.gov Identifier:
NCT01243476
First received: November 17, 2010
Last updated: July 21, 2014
Last verified: July 2014
  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).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Lenalidomide
Other: Placebo
Phase 3

Study Type: 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
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.

Resource links provided by NLM:


Further study details as provided by Fundación General de la Universidad de Salamanca:

Primary Outcome Measures:
  • Period until the progression of myelodysplastic syndrome [ Time Frame: 6 years (study treatment and follow up) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Erythroid response [ Time Frame: 6 years (study treatment and follow up) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Cytogenetic response [ Time Frame: 6 years (study treatment and follow up) ] [ Designated as safety issue: No ]
    Cytogenetic response according to the Criteria of the MDS International Work Team.

  • Bone marrow response [ Time Frame: 6 years (study treatment and follow up) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
  • Time from diagnose to transfusion independence. [ Time Frame: 6 years (study treatment and follow up) ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2010
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lenalidomide
Experimental treatment branch with Lenalidomide 5 mg/day (oral use)
Drug: Lenalidomide
Treatment with Revlimid (lenalidomide), oral use, 5 mg daily during study treatment (104 weeks).
Other Name: Revlimid 5 mg
Placebo Comparator: placebo
Placebo branch (oral use)
Other: Placebo
Placebo, oral use, daily during study treatment (104 weeks)
Other Name: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243476

Locations
Spain
Hospital de Cabueñes Terminated
Gijón, Asturias, Spain, 33394
Hospital Central de Asturias Recruiting
Oviedo, Asturias, Spain, 33006
Contact: Teresa Bernal del Castillo, MD    0034 985 108 000 ext 39179    bernaldelcastillo@gmail.com   
Principal Investigator: Teresa Bernal del Castillo, MD         
Hospital Universitari Germans Trias i Pujol (ICO Badalona) Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Blanca Xicoy Cirici, MD    0034 93 497 89 24    bxicoyc@comb.es   
Principal Investigator: Blanca Xicoy Cirici, MD         
Hospital Son Llàtzer Recruiting
Palma de Mallorca, Islas Baleares, Spain, 07198
Contact: Joan Bargay Lleonart, MD    0034 871 20 21 38    jbargay@hsll.es   
Principal Investigator: Joan Bargay Lleonart, MD         
Hospital de Cruces Recruiting
Barakaldo, Vizcaya, Spain, 48930
Contact: Beatriz Arrizabalaga Amuchastegui, MD    0034 946 00 60 89    BEATRIZ.ARRIZABALAGAAMUCHASTEG@osakidetza.net   
Principal Investigator: Beatriz Arrizabalaga Amuchastegui, MD         
Hospital Clínic i Provincial Recruiting
Barcelona, Spain, 08036
Contact: Benet Nomdedeu Tobella, MD    0034 93 227 54 00 ext 2805    nomdedeu@clinic.ub.es   
Principal Investigator: Benet Nomdedeu Tobella, MD         
Hospital Universitario Reina Sofía Recruiting
Córdoba, Spain, 14004
Contact: Joaquín Sánchez García, MD    0034 957 010 176    joaquin.sanchez@cheerful.com   
Principal Investigator: Joaquín Sánchez García, MD         
Hospital Infanta Leonor Recruiting
Madrid, Spain, 28031
Contact: José Angel Hernandez Rivas, MD    0034 911918507    jahernandezr@salud.madrid.org   
Principal Investigator: José Angel Hernandez Rivas, MD         
Hospital Clínico San Carlos Terminated
Madrid, Spain, 28040
Hospital Universitario La Paz Terminated
Madrid, Spain, 28046
Hospital General Universitario José Maria Morales Meseguer Recruiting
Murcia, Spain, 30008
Contact: Maria Luz Amigo Lozano, MD    0034 968 36 09 00    mluzamigo@yahoo.es   
Principal Investigator: Mª Luz Amigo Lozano, MD         
Hospital Clínico Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Contact: María Díez Campelo, MD    0034 923 29 13 16    mdiezcampelo@usal.es   
Principal Investigator: María Díez Campelo, MD         
Hospital Universitario Virgen del Rocío Terminated
Sevilla, Spain, 41013
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46009
Contact: Guillermo Sanz Santillana, MD    0034 96 386 27 09    sanz_gui@gva.es   
Principal Investigator: Guillermo Sanz Santillana, MD         
Sponsors and Collaborators
Fundación General de la Universidad de Salamanca
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
  More Information

Publications:
List A, Gordon W, Dewald G, Bennett J, Giagounidis A, Raza A et al. Long-term clinical benefit of lenalidomide (Revlimid) treatment in patients with myelodysplastic syndrome and chromosome deletion 5q [Abstract]. Blood. 2006;108:251A.
Mallo M, Cervera J et al. Prognostic impact of additional chromosomal aberrations to 5q- in patients with primary myelodysplastic syndromes. Oral comunication, 0906, 13th Congress of the European Hematology Association. Haematologica / 2008; 93(s1), pag. 360
List, AF. Active treatment-improving outcomes in del 5q patients. Leukemia Research, (2007)31(Suppl. 1), S9.

Responsible Party: Fundación General de la Universidad de Salamanca
ClinicalTrials.gov Identifier: NCT01243476     History of Changes
Other Study ID Numbers: SINTRA-REV, 2009-013619-36
Study First Received: November 17, 2010
Last Updated: July 21, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Fundación General de la Universidad de Salamanca:
myelodysplastic syndrome
5q deletion
anemia
lenalidomide
red blood cells transfusion

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014