Lenalidomide in High-Risk MDS and AML With Del(5q) or Monosomy 5 - Full Text View

Sponsor:	Nordic MDS Group
Information provided by:	Nordic MDS Group
ClinicalTrials.gov Identifier:	NCT00761449

Purpose

The aim of this study is to investigate the efficacy of lenalidomide in high risk MDS or AML with chromosome 5 aberrations.

Condition	Intervention	Phase
MDS AML	Drug: lenalidomide	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multicentre Phase II Study of the Efficacy and Safety of Lenalidomide in High-Risk Myeloid Disease (High-Risk MDS and AML) With a Karyotype Including Del(5q) or Monosomy 5

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome tetrasomy 18p

Drug Information available for: Lenalidomide CC 5013

U.S. FDA Resources

Further study details as provided by Nordic MDS Group:

Primary Outcome Measures:

Major cytogenetic response (50% or more reduction of the del5(q) or monosomy 5 FISH positive clone in the bone marrow using the LSI EGR1/D5S23,D5S721 FISH probe) after 16 weeks of lenalidomide treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Minor and complete cytogenetic (FISH) response after 8 and 16 weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Red blood cell transfusion independence [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Erythroid response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Bone marrow response (morphology) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Modification of gene expression profiling during treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Safety [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	October 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 1. lenalidomide	Drug: lenalidomide Initial dose is oral lenalidomide 10 mg daily continuously. The dose should be increased to 20 mg day 1 in week 6 and to 30 mg day 1 in week 10. This dose should be kept for seven weeks. Thus, the total study period is 16 weeks. Other Name: Revlimid

Detailed Description:

Previous studies have shown that the immunomodulatory drug lenalidomide is effective in the treatment of low risk MDS with del(5q). Treatment of this subgroup of MDS patients resulted in 67% major erythroid responses and 45% complete cytogenetic responses. We therefore intend to test the efficacy of lenalidomide in a group of high-risk patients who are ineligible for conventional chemotherapy and who have a dismal prognosis. The patients must have a karyotype including del(5q) but patients with a karyotype including monosomy 5 are also eligible. We hypothesize that hight risk MDS or AML patients with other chromosomal aberrations than del(5q) can be affected by the lenalidomide effect.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Must be >18 years of age at the time of signing the informed consent form
MDS at IPSS Int-2 or High with a karyotype including del(5q) or monosomy 5 confirmed with FISH (using the LSI EGR1/D5S23,D5S721 FISH probe)
Acute myeloid leukemia with a karyotype including del(5q) or monosomy 5 confirmed with FISH (using the LSI EGR1/D5S23,D5S721 FISH probe)
Patients could be included if:
At diagnosis and not considered eligible for induction chemotherapy
Refractory to induction therapy
Relapse after induction chemotherapy leading to CR and considered not eligible for reinduction
Relapse after allogeneic stem cell transplantation and not considered suitable for reinduction chemotherapy or other conventional relapse therapy.
Subject has signed the informed consent document.
Women of childbearing potential, WCBP, must agree to practice complete abstinence from heterosexual intercourse or to use two methods of contraception beginning 4 weeks prior to the start of the study medication, while on study medication and 4 weeks after the last dose of study medication. WCBP must have two negative serum or urine pregnancy tests prior to starting study drug. WCBP must agree to have pregnancy tests weekly for the first 4 weeks and then every 4 weeks while on study medication and 4 weeks after the last dose of study medication.
Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on study medication and 4 weeks after the last dose of study medication.

Exclusion Criteria:

Pregnant or lactating females.
Prior therapy with lenalidomide
Patients who are eligible for curative treatment
Expected survival less than two months.
Acute promyelocytic leukemia (APL)
Absolute peripheral blast count >30,000/mm3
Central nervous system leukemia
Serum biochemical values as follows
Serum creatinine >2.0 mg/dL (177 micromol/L)
Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
Serum total bilirubin >1.5 mg/dL (26 micromol/L)
Prior allergic reaction to thalidomide
Uncontrolled systemic infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761449

Contacts

Contact: Lars Möllgård, MD, PhD	+46 8 58582514	lars.mollgard@karolinska.se
Contact: Eva Hellström-Lindberg, MD, PhD	+46 8 585 825 06	Eva.Hellstrom-Lindberg@ki.se

Locations

Denmark
Department of Hematology, Aalborg Hospital	Recruiting
Aalborg, Denmark, 9000
Department of Hematology, Aarhus University Hospital	Recruiting
Aarhus, Denmark, 8000
Department of Hematology, Rigshospitalet	Recruiting
Copenhagen, Denmark, 2100
Department of Hematology, Herlev Hospital	Recruiting
Herlev, Denmark, 2730
Department of Hematology, Odense University Hospital	Recruiting
Odense, Denmark, 5000
Department of Hematology, Vejle Hospital	Recruiting
Vejle, Denmark, 7100
Norway
Department of Hematology, Rikshospitalet University Hospital	Recruiting
Oslo, Norway, 0027
Department of Medicine, Ullevål Hospital	Recruiting
Oslo, Norway, 0407
Department of Hematology, Trondheim University Hospital	Recruiting
Trondheim, Norway, 7006
Sweden
Department of Hematology and Coagulation, Sahlgrenska University hospital	Recruiting
Gothenburg, Sweden, 413 45
Department of Hematology, Lund University Hospital	Recruiting
Lund, Sweden, 221 85
Department of Hematology, Malmö University Hospital	Recruiting
Malmö, Sweden, 205 02
Hematology Center, Karolinska University Hospital Solna	Recruiting
Stockholm, Sweden, 171 76
Hematology Center, Karolinska University Hospital Huddinge	Recruiting
Stockholm, Sweden, 141 86
Contact: Lars Möllgård, MD, PhD +46 8 58582514 lars.mollgard@karolinska.se
Principal Investigator: Lars Möllgård, MD, PhD
Department of Medicine, Sundsvall Hospital	Recruiting
Sundsvall, Sweden, 851 86
Department of Medicine, Umeå University Hospital	Recruiting
Umeå, Sweden, 901 85
Department of Hematology, Akademiska University Hospital	Recruiting
Uppsala, Sweden, 751 85
Department of Medicine, Örebro University Hospital	Recruiting
Örebro, Sweden, 701 85

Sponsors and Collaborators

Nordic MDS Group

Investigators

Principal Investigator:

Eva Hellström-Lindberg, MD, PhD

Nordic MDS Group

More Information

Additional Information:

Nordic MDS Group website This link exits the ClinicalTrials.gov site

No publications provided by Nordic MDS Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Möllgård L, Saft L, Treppendahl MB, Dybedal I, Nørgaard JM, Astermark J, Ejerblad E, Garelius H, Dufva IH, Jansson M, Jädersten M, Kjeldsen L, Linder O, Nilsson L, Vestergaard H, Porwit A, Grønbæk K, Lindberg EH. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. Haematologica. 2011 Jul;96(7):963-71.

Responsible Party:	Dr Eva Hellström Lindberg, MD, PhD, Nordic MDS Group
ClinicalTrials.gov Identifier:	NCT00761449 History of Changes
Other Study ID Numbers:	NMDSG07A, EudraCT no: 2007-000450-31
Study First Received:	September 26, 2008
Last Updated:	September 29, 2008
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Nordic MDS Group:

MDS
AML
Lenalidomide
monosomy 5
del5q

Additional relevant MeSH terms:

Monosomy
Aneuploidy
Chromosome Aberrations
Pathologic Processes
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 February 09, 2012