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

Sponsor

Nordic MDS Group (Other)

Overall Status

Completed

CT.gov ID

NCT00761449

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
MDS AML	Drug: lenalidomide	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

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

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

Outcome Measures

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 [16 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Department of Hematology, Aalborg Hospital	Aalborg	Denmark	9000
2	Department of Hematology, Aarhus University Hospital	Aarhus	Denmark	8000
3	Department of Hematology, Rigshospitalet	Copenhagen	Denmark	2100
4	Department of Hematology, Herlev Hospital	Herlev	Denmark	2730
5	Department of Hematology, Odense University Hospital	Odense	Denmark	5000
6	Department of Hematology, Vejle Hospital	Vejle	Denmark	7100
7	Department of Hematology, Rikshospitalet University Hospital	Oslo	Norway	0027
8	Department of Medicine, Ullevål Hospital	Oslo	Norway	0407
9	Department of Hematology, Trondheim University Hospital	Trondheim	Norway	7006
10	Department of Hematology and Coagulation, Sahlgrenska University hospital	Gothenburg	Sweden	413 45
11	Department of Hematology, Lund University Hospital	Lund	Sweden	221 85
12	Department of Hematology, Malmö University Hospital	Malmö	Sweden	205 02
13	Hematology Center, Karolinska University Hospital Huddinge	Stockholm	Sweden	141 86
14	Hematology Center, Karolinska University Hospital Solna	Stockholm	Sweden	171 76
15	Department of Medicine, Sundsvall Hospital	Sundsvall	Sweden	851 86
16	Department of Medicine, Umeå University Hospital	Umeå	Sweden	901 85
17	Department of Hematology, Akademiska University Hospital	Uppsala	Sweden	751 85
18	Department of Medicine, Örebro University Hospital	Örebro	Sweden	701 85