Myelodysplastic syndrome and acute myeloid leukemia with a deletion of 5q MedDRA version: 14.1 Level: LLT Classification code 10067096 Term: 5q minus myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
NMDSG Nordics Myeloplastics Syndrom Study Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study (del(5q) confirmed by FISH in all cases): • 18 years of age or older at the time of signing the informed consent form. • MDS with IPSS Int-2 or High with a karyotype including del(5q). • Acute myeloid leukaemia (AML) with multilineage dysplasia and 20-30 % blasts (former RAEB-t) with a karyotype including del(5q). • Subject has signed the informed consent form. • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test prior to starting lenalidomide. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, patches, or implantable hormonal contraceptive methods; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasecomized partner) while on lenalidomide. WCBP must agree to have pregnancy tests every 4 weeks while on lenalidomide. • Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on lenalidomide, when temporarily stopping lenalidomide and 28 days after the last dose of lenalidomide. Note: Refractory and relapsed patients can be included as long as they fulfil the inclusion criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Eligible for upfront allogeneic SCT without prior induction chemotherapy or azacitidine • Pregnant or lactating females. • Prior therapy with azacitidine • Prior therapy with lenalidomide • Expected survival less than two months. • Acute promyelocytic leukemia (APL) • Central nervous system leukemia • Serum biochemical values as follows 1. Serum creatinine >2.0 mg/dL (177 mmol/L) 2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transferase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN) 3. Serum total bilirubin >1.5 mg/dL • Prior allergic reaction to thalidomide • Uncontrolled systemic infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the efficacy of azacitidine with or without the additioiin of lenalidomide in high-risk MDS (IPSS Int-2 or high) and AML (multilineage dysplasia and 20-30% marrow blasts) with a karyotype oncluding del(5q);Secondary Objective: To study the safety of the combination of lenalidomide andd azaciticine in high-risk MDS (IPSS Int-2 or high) and AML (multilineage dysplasia and 20-30% marrow blasts) with a karyotype oncluding del(5q);Primary end point(s): Response according to IWG criteria for MDS and AML;Timepoint(s) of evaluation of this end point: After 6 cycles of azacitidine or azacitidine+lenalidomide treatment, or at end of study if this occurs at an earlier time point | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Cytogenetic response after 3 cycles (FISH using the LSI EGR1/D5S23,D5S721 FISH probe) and 6 cycles (karyotype) of azacitidine or azacitidine+lenalidomide treatment, or at end of study (karyotype) if this occurs at an earlier time point. ;Secondary end point(s): Cytogenetic response (FISH and karyotype) Safety in azacitidine vs azacitidine + lenalidomide groups Azacitidine cycle interval between groups Survival in azacitidine vs azacitidine + lenalidomide groups Relapse in azacitidine vs azacitidine + lenalidomide groups Analysis of a broad spectrum of molecular and cellular events which previously have been identified as related to MDS with del(5q). These events will be used to a) identify potential biomarkers for response and b) to evaluate the effect of treatment on stem cells with specific biological patterns, e.g “quality of response”. Biological analyses encompass screening for candidate gene mutations, gene, miRNA and protein expression, methylation and histone acetylation patterns, stem cell biology and telomere status (21, 22, 23). | — |
Countries
Denmark, Finland, Norway, Sweden
Contacts
Public ContactLars Möllgård
Karolinska University Hospital
Outcome results
None listed