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

AML Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00761449
• Other study ID #: NMDSG07A
• Secondary ID: EudraCT no: 2007
• Status: Completed
• Phase: Phase 2
• First received: September 26, 2008
• Last updated: April 26, 2012
• Start date: October 2007
• Est. completion date: December 2009

Study information

• Verified date: January 2010
• Source: Nordic MDS Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AML
• MDS

Intervention

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.

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aalborg Hospital	Aalborg
Denmark	Department of Hematology, Aarhus University Hospital	Aarhus
Denmark	Department of Hematology, Rigshospitalet	Copenhagen
Denmark	Department of Hematology, Herlev Hospital	Herlev
Denmark	Department of Hematology, Odense University Hospital	Odense
Denmark	Department of Hematology, Vejle Hospital	Vejle
Norway	Department of Hematology, Rikshospitalet University Hospital	Oslo
Norway	Department of Medicine, Ullevål Hospital	Oslo
Norway	Department of Hematology, Trondheim University Hospital	Trondheim
Sweden	Department of Hematology and Coagulation, Sahlgrenska University hospital	Gothenburg
Sweden	Department of Hematology, Lund University Hospital	Lund
Sweden	Department of Hematology, Malmö University Hospital	Malmö
Sweden	Department of Medicine, Örebro University Hospital	Örebro
Sweden	Hematology Center, Karolinska University Hospital Huddinge	Stockholm
Sweden	Hematology Center, Karolinska University Hospital Solna	Stockholm
Sweden	Department of Medicine, Sundsvall Hospital	Sundsvall
Sweden	Department of Medicine, Umeå University Hospital	Umeå
Sweden	Department of Hematology, Akademiska University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Nordic MDS Group

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Minor and complete cytogenetic (FISH) response after 8 and 16 weeks		16 weeks	No
Secondary	Red blood cell transfusion independence		16 weeks	No
Secondary	Erythroid response		16 weeks	No
Secondary	Bone marrow response (morphology)		16 weeks	No
Secondary	Modification of gene expression profiling during treatment		16 weeks	No
Secondary	Safety		16 weeks	Yes

External Links

•   Nordic MDS Group website