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

NCT01243476 | Completed Phase 3

• 2 other identifiers: SINTRA-REV2009-013619-36
• Study Type: interventional
• Target: 61
• Locations: 3 countries
• Sites: 25

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).

Conditions

Myelodysplastic Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (9)

• Erythroid response

  6 years (study treatment and follow up)

• Duration of the red blood cells transfusion independency

  6 years (study treatment and follow up)

• Change of the hemoglobin concentration (Hb) in relation to baseline levels

  6 years (study treatment and follow up)

• Variation in platelets and neutrophils absolute count in relation to baseline levels

  6 years (study treatment and follow up)

• Cytogenetic response

  6 years (study treatment and follow up)

Study Arms (2)

lenalidomide

EXPERIMENTAL

Experimental treatment branch with Lenalidomide 5 mg/day (oral use)

Drug: Lenalidomide

placebo

PLACEBO COMPARATOR

Placebo branch (oral use)

Other: Placebo

Interventions

Lenalidomide DRUG

Treatment with Revlimid (lenalidomide), oral use, 5 mg daily during study treatment (104 weeks).

Also known as: Revlimid 5 mg

lenalidomide

Placebo OTHER

Placebo, oral use, daily during study treatment (104 weeks)

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- The patient must, in the investigator's opinion, be able to comply with all the clinical trial requirements.
• \- 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.
• \- Age \> 18 years.
• \- 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.
• \- 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.
• \- The patient must have an ECOG performance status of ≤ 2.
• \- The patient must be able to comply with the scheduled study visits.
• \- 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.
• \- All male patients must:

You may not qualify if:

• \- Any organic disease or psychiatric disorder which makes it impossible for the patient to sign or understand the informed consent.
• \- Having received any treatment for MDS.
• \- Del(5q) MDS with transfusion-dependent anaemia, and documented confirmation that the patient has received any pRBC transfusion due to the underlying condition (MDS).
• \- Pregnant or breast-feeding women.
• \- 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.
• \- 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.
• \- Known hypersensitivity to or a history of uncontrollable side effects to lenalidomide.

Sponsors & Collaborators

• Fundación General de la Universidad de Salamanca: lead
• Celgene Corporation: collaborator

Study Sites (25)

Hôpitaux Universitaires de Strasbourg

Strasbourg, Bajo Rin, 67091, France

Location

Centre Hospitalier Universitaire de Nîmes

Nîmes, Gard, 30900, France

Location

Centre Hospitalier Régional d'Orléans

Orléans, Loiret, 45100, France

Location

Centre Hospitalier Universitaire d'Angers

Angers, Maine Y Loira, 49100, France

Location

Centre Hospitalier Universitaire Brabois

Nancy, Meurthe Y Mosel, 54500, France

Location

Centre Hospitalier d'Avignon

Avignon, Vaucluse, 84000, France

Location

Hôspital St. Louis

Paris, 75010, France

Location

Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden

Dresden, 01307, Germany

Location

Marien Hospital Duesseldorf

Düsseldorf, 40479, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Hospital Son Llàtzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Hospital Universitari Germans Trias i Pujol (ICO Badalona)

Badalona, Barcelona, 08916, Spain

Location

Hospital de Cabueñes

Gijón, Principality of Asturias, 33394, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48930, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Instituto Catalán de Oncología de Gerona

Girona, 17007, Spain

Location

Hospital Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General Universitario José Maria Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Related Publications (14)

• Steensma DP, Tefferi A. The myelodysplastic syndrome(s): a perspective and review highlighting current controversies. Leuk Res. 2003 Feb;27(2):95-120. doi: 10.1016/s0145-2126(02)00098-x.

  PMID: 12526916 BACKGROUND

• Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.

  PMID: 9058730 BACKGROUND

• List AF. New approaches to the treatment of myelodysplasia. Oncologist. 2002;7 Suppl 1:39-49. doi: 10.1634/theoncologist.7-suppl_1-39.

  PMID: 11961208 BACKGROUND

• McHugh SM, Deighton J, Stewart AG, Lachmann PJ, Ewan PW. Bee venom immunotherapy induces a shift in cytokine responses from a TH-2 to a TH-1 dominant pattern: comparison of rush and conventional immunotherapy. Clin Exp Allergy. 1995 Sep;25(9):828-38. doi: 10.1111/j.1365-2222.1995.tb00025.x.

  PMID: 8564721 BACKGROUND

• Bellamy WT. Expression of vascular endothelial growth factor and its receptors in multiple myeloma and other hematopoietic malignancies. Semin Oncol. 2001 Dec;28(6):551-9. doi: 10.1016/s0093-7754(01)90023-5.

  PMID: 11740808 BACKGROUND

• Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004 Apr;4(4):314-22. doi: 10.1038/nrc1323. No abstract available.

  PMID: 15057291 BACKGROUND

• List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. doi: 10.1056/NEJMoa041668.

  PMID: 15703420 BACKGROUND

• List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65. doi: 10.1056/NEJMoa061292.

  PMID: 17021321 BACKGROUND

• 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.

  BACKGROUND

• 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

  BACKGROUND

• Fenaux P, Kelaidi C. Treatment of the 5q- syndrome. Hematology Am Soc Hematol Educ Program. 2006:192-8. doi: 10.1182/asheducation-2006.1.192.

  PMID: 17124060 BACKGROUND

• Kelaidi C, Eclache V, Fenaux P. The role of lenalidomide in the management of myelodysplasia with del 5q. Br J Haematol. 2008 Feb;140(3):267-78. doi: 10.1111/j.1365-2141.2007.06910.x.

  PMID: 18217896 BACKGROUND

• List, AF. Active treatment-improving outcomes in del 5q patients. Leukemia Research, (2007)31(Suppl. 1), S9.

  BACKGROUND

• Diez-Campelo M, Lopez-Cadenas F, Xicoy B, Lumbreras E, Gonzalez T, Del Rey Gonzalez M, Sanchez-Garcia J, Coll Jorda R, Slama B, Hernandez-Rivas JA, Thepot S, Bernal T, Guerci-Bresler A, Bargay J, Amigo ML, Preudhomme C, Fenwarth L, Platzbecker U, Gotze KS, Arar A, Toribio S, Del Canizo C, Hernandez-Rivas JM, Fenaux P. Low dose lenalidomide versus placebo in non-transfusion dependent patients with low risk, del(5q) myelodysplastic syndromes (SintraREV): a randomised, double-blind, phase 3 trial. Lancet Haematol. 2024 Sep;11(9):e659-e670. doi: 10.1016/S2352-3026(24)00142-X. Epub 2024 Jul 18.

  PMID: 39033767 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Consuelo del Cañizo, MD

  Hospital Clínico Universitario de Salamanca

  STUDY CHAIR

• María Díez Campelo, MD

  Hospital Clínico Universitario de Salamanca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 18, 2010
• Study Start: January 1, 2010
• Primary Completion: June 6, 2022
• Study Completion: June 6, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-01

Locations

FR (7); DE (3); ES (15)