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

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

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

Study Overview

• Status: Completed
• Conditions: AML; MDS
• Intervention / Treatment: Drug: lenalidomide

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Hematology, Aalborg Hospital
  • Aarhus, Denmark, 8000
    • Department of Hematology, Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Department of Hematology, Rigshospitalet
  • Herlev, Denmark, 2730
    • Department of Hematology, Herlev Hospital
  • Odense, Denmark, 5000
    • Department of Hematology, Odense University Hospital
  • Vejle, Denmark, 7100
    • Department of Hematology, Vejle Hospital
• Norway
  • Oslo, Norway, 0027
    • Department of Hematology, Rikshospitalet University Hospital
  • Oslo, Norway, 0407
    • Department of Medicine, Ullevål Hospital
  • Trondheim, Norway, 7006
    • Department of Hematology, Trondheim University Hospital
• Sweden
  • Gothenburg, Sweden, 413 45
    • Department of Hematology and Coagulation, Sahlgrenska University hospital
  • Lund, Sweden, 221 85
    • Department of Hematology, Lund University Hospital
  • Malmö, Sweden, 205 02
    • Department of Hematology, Malmö University Hospital
  • Stockholm, Sweden, 141 86
    • Hematology Center, Karolinska University Hospital Huddinge
  • Stockholm, Sweden, 171 76
    • Hematology Center, Karolinska University Hospital Solna
  • Sundsvall, Sweden, 851 86
    • Department of Medicine, Sundsvall Hospital
  • Umeå, Sweden, 901 85
    • Department of Medicine, Umeå University Hospital
  • Uppsala, Sweden, 751 85
    • Department of Hematology, Akademiska University Hospital
  • Örebro, Sweden, 701 85
    • Department of Medicine, Örebro University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Nordic MDS Group
• Investigators: Principal Investigator: Eva Hellström-Lindberg, MD, PhD, Nordic MDS Group

Publications and helpful links

General Publications

• 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. Erratum In: Haematologica. 2011 Aug;96(8):1240. Lindberg, Eva Hellstrom [corrected to Hellstrom-Lindberg, Eva].

Helpful Links

• Nordic MDS Group website

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 26, 2008
• First Submitted That Met QC Criteria: September 26, 2008
• First Posted (Estimate): September 29, 2008

Study Record Updates

• Last Update Posted (Estimate): April 27, 2012
• Last Update Submitted That Met QC Criteria: April 26, 2012
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: AML; Lenalidomide; MDS; monosomy 5; del5q
• Additional Relevant MeSH Terms: Pathologic Processes; Chromosome Aberrations; Aneuploidy; Monosomy; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: NMDSG07A; EudraCT no: 2007-000450-31