Higher-Risk Myelodysplastic Syndromes (MDS) (IPSS Risk: High or INT-2) MedDRA version: 14.1 Level: LLT Classification code 10002311 Term: Anemia refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 10028532 Term: Myelodysplasia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: REVLIMID*21CPS 10MG
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
AZIENDA OSPEDALIERA DI BOLOGNA POLICLINICO S. ORSOLA M. MALPIGHI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A. Male and female patients = 18 years B. Signed informed consent C. Confirmed diagnosis of MDS according to WHO 2008 classification D. IPSS risk Int-2 or High proved by bone marrow aspiration, biopsy and cytogenetics E. Karnofsky score > 60% at study entry F. Adequate renal, pulmonary and hepatic function, intended as follows: • Bilirubin = 2.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction) • AST and ALT = 3.5 times ULN • Creatinine = 2 times ULN G. HIV negativity H. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in Appendix 1 and pregnancy results must be negative. I. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in Appendix 1 J. Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in Appendix 1 K. Males must agree not to donate semen or sperm during the duration specified in Appendix 1 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: A. Prior treatment with Azacitidine or Lenalidomide. B. Any prior chemotherapy or radiotherapy for another malignancy within 6 months C. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for = 3 years. However, subjects with the following history/concurrent conditions may enroll at any time: • Basal cell carcinoma of the skin • Carcinoma in situ of the cervix • Incidental histologic finding of prostate cancer (Tumor Node Metastasis (TNM) stage of T1a or T1b) D. Concurrent chemotherapy for another malignancy E. Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection. F. Any of the following laboratory abnormalities: • Serum aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.5 x upper limit of normal (ULN) • Serum bilirubin levels > 2.5 x ULN; serum bilirubin levels > 2.5 x ULN are acceptable if these can be attributed to active hemolysis (as indicated by positive direct Coombs’ testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase), or ineffective erythropoiesis (as indicated by bone marrow findings) • Creatinine > 2 times ULN G. Uncontrolled hyperthyroidism or hypothyroidism. H. Absence of patient’s written informed consent I. Current uncontrolled severe infections
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the feasibility of the combination Azacitidine + Lenalidomide vs the sequential use of Azacitidine and Lenalidomide in high risk Myelodysplastic Syndromes (MDS) (IPSS score risk : High or INT-2) patients.;Secondary Objective: A. The safety of the combination regimen vs the sequential use, considered as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory values following therapy B. The quality of responses C. The progression to AML in the 2 different treatment strategies D. OS benefits between in the combination and the sequence arms To determine: • The relationship of cytogenetic abnormalities and response to treatment • Biomarkers of the response;Primary end point(s): The Overall Response Rate: defined as the Rate of Complete Remission (CR), Partial Remission (PR) and Hematological Improvement (HI), following the International Working Group (IWG) criteria (Cheson BD et al, Blood 2000, and Blood 2006);Timepoint(s) of evaluation of this end point: 24 months (maximum period for the treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A. The rate of Complete Remission (CR), following the International Working Group (IWG) criteria (Cheson BD et al, Blood 2006) B. The duration of responses C. The overall survival;Timepoint(s) of evaluation of this end point: 48 months (24 months follow-up forseen) | — |
Countries
Italy
Contacts
Public ContactU.O. Ematologia (Baccarani):Finelli
AOU di Bologna, Policlinico S.Orsola-Malpighi
Outcome results
None listed