Lenalidomide in High-risk MDS and AML With Del(5q) or Monosomy 5

Phase 2

Completed

• Conditions: MDS; AML
• Interventions: Drug: lenalidomide

• Registration Number: NCT00761449
• Lead Sponsor: Nordic MDS Group

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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2008-09-26
• Study First Submitted QC: 2008-09-26
• Study First Posted: 2008-09-29
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Status Verified: 2010-01
• Last Update Submitted: 2012-04-26
• Last Update Posted: 2012-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	lenalidomide	1. lenalidomide

Primary Outcome Measures

Name	Time	Method
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	16 weeks

Secondary Outcome Measures

Name	Time	Method
Minor and complete cytogenetic (FISH) response after 8 and 16 weeks	16 weeks
Red blood cell transfusion independence	16 weeks
Erythroid response	16 weeks
Bone marrow response (morphology)	16 weeks
Modification of gene expression profiling during treatment	16 weeks
Safety	16 weeks

Trial Locations

Locations (18)

Department of Hematology, Aalborg Hospital; 🇩🇰 Aalborg, Denmark

Department of Hematology, Herlev Hospital; 🇩🇰 Herlev, Denmark

Department of Hematology, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Department of Hematology, Malmö University Hospital; 🇸🇪 Malmö, Sweden

Hematology Center, Karolinska University Hospital Huddinge; 🇸🇪 Stockholm, Sweden

Department of Hematology, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Hematology, Vejle Hospital; 🇩🇰 Vejle, Denmark

Department of Hematology and Coagulation, Sahlgrenska University hospital; 🇸🇪 Gothenburg, Sweden

Department of Hematology, Rikshospitalet University Hospital; 🇳🇴 Oslo, Norway

Department of Hematology, Trondheim University Hospital; 🇳🇴 Trondheim, Norway

Department of Hematology, Odense University Hospital; 🇩🇰 Odense, Denmark

Department of Hematology, Lund University Hospital; 🇸🇪 Lund, Sweden

Department of Medicine, Umeå University Hospital; 🇸🇪 Umeå, Sweden

Hematology Center, Karolinska University Hospital Solna; 🇸🇪 Stockholm, Sweden

Department of Medicine, Sundsvall Hospital; 🇸🇪 Sundsvall, Sweden

Department of Medicine, Örebro University Hospital; 🇸🇪 Örebro, Sweden

Department of Hematology, Akademiska University Hospital; 🇸🇪 Uppsala, Sweden

Department of Medicine, Ullevål Hospital; 🇳🇴 Oslo, Norway