Clinical trial NCT00761449: Lenalidomide in High-risk MDS and AML With Del(5q) or Monosomy 5
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MDS
AML
Keywords: MDS
AML
Lenalidomide
monosomy 5
del5q
Lead sponsor: Nordic MDS Group
Sponsor class: NETWORK
First posted: 2008-09-29
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: 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
timeFrame: 16 weeks
Secondary outcomes:
measure: Minor and complete cytogenetic (FISH) response after 8 and 16 weeks
timeFrame: 16 weeks
measure: Red blood cell transfusion independence
timeFrame: 16 weeks
measure: Erythroid response
timeFrame: 16 weeks
measure: Bone marrow response (morphology)
timeFrame: 16 weeks
measure: Modification of gene expression profiling during treatment
timeFrame: 16 weeks
measure: Safety
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Hematology, Aalborg Hospital
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Hematology, Rigshospitalet
city: Herlev
country: Denmark
facility: Department of Hematology, Herlev Hospital
city: Odense
country: Denmark
facility: Department of Hematology, Odense University Hospital
city: Vejle
country: Denmark
facility: Department of Hematology, Vejle Hospital
city: Oslo
country: Norway
facility: Department of Hematology, Rikshospitalet University Hospital
city: Oslo
country: Norway
facility: Department of Medicine, Ullevål Hospital
city: Trondheim
country: Norway
facility: Department of Hematology, Trondheim University Hospital
city: Gothenburg
country: Sweden
facility: Department of Hematology and Coagulation, Sahlgrenska University hospital
city: Lund
country: Sweden
facility: Department of Hematology, Lund University Hospital
city: Malmö
country: Sweden
facility: Department of Hematology, Malmö University Hospital
city: Stockholm
country: Sweden
facility: Hematology Center, Karolinska University Hospital Huddinge
city: Stockholm
country: Sweden
facility: Hematology Center, Karolinska University Hospital Solna
city: Sundsvall
country: Sweden
facility: Department of Medicine, Sundsvall Hospital
city: Umeå
country: Sweden
facility: Department of Medicine, Umeå University Hospital
city: Uppsala
country: Sweden
facility: Department of Hematology, Akademiska University Hospital
city: Örebro
country: Sweden
facility: Department of Medicine, Örebro University Hospital
Study officials:
affiliation: Nordic MDS Group
name: Eva Hellström-Lindberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mollgard L, Saft L, Treppendahl MB, Dybedal I, Norgaard JM, Astermark J, Ejerblad E, Garelius H, Dufva IH, Jansson M, Jadersten M, Kjeldsen L, Linder O, Nilsson L, Vestergaard H, Porwit A, Gronbaek K, Hellstrom-Lindberg E. 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. doi: 10.3324/haematol.2010.039669.