Myelodysplastic Syndrome(MDS) / Acute Myeloid Leukemia(AML) MedDRA version: 9.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome
Conditions
Interventions
Trade Name: Lenalidomide (Revlimid®)
Pharmaceutical Form: Capsule*
Trade Name: azacitidine (Vidaza®)
Product Name: azacitidine
Pharmaceutical Form: Suspension for injection
Sponsors
Groupe Francophone des Myélodysplasies (GFM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1.Age = 18 years 2.Must understand and voluntarily sign an informed consent form 3.Must Especially in the case of AML: Patient considered ineligible for intensive chemotherapy due to age, cardiac contraindication to anthracyclines, comorbidities, previous failure of intensive chemotherapy, or patient willing to avoid intensive chemotherapy 4.Must be able to adhere to the study visit schedule and other protocol requirements 5.Prior Thalidomid allowed 6.Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, or AML 7.with an associated del 5q[31] (the deleted chromosomal region must include 5q[31]), with or without additional cytogenetic abnormalities 8.Female subjects of chilbearing potential* must : - Understand the study drug is expected to have a teratogenic risk. - - Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment. - Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These pregnancy tests should be performed on the day of the study visit or in the 3 days prior to the study visit. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. - Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy even if she has amenorrhoea. This applies unless the subject commits to absolute and continuous abstinence confirmed on a monthly basis, to avoid pregnancy for the duration of study. If not established on effective contraception, the female subject must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated. Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended. If a female subject is currently using combined oral contraception, the patient should switch to one of the effective methods listed above. The risk of venous thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone. Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia . Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or thrombocytopenia. - Understand that even if she has amenorrhea, she must follow all the advice on effective contraception. - She understands
Exclusion criteria
Exclusion criteria: Exclusion criteria 1.Pregnant or lactating females. 2.Proliferative (WBC = 13,000/mL) Chronic Myelomonocytic Leukaemia(CMML) 3.Prior = grade-2 NCI CTCAE (v 3.0) allergic reaction to thalidomide. 4.Prior desquamating (blistering) rash while taking thalidomide. 5.Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for = 3 years. 6.Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days, with the exception of hydroxyurea in case of high WBC counts 7.Less than 6 months since prior allogeneic bone marrow transplantation. 8.Less than 3 months since prior autologous bone marrow or stem cell transplantation. 9.Recombinant human erythropoietin (rHuEPO) therapy received within 28 days. 10.Known HIV-1 positivity. 11.Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study. 12.Any of the following laboratory abnormalities: •Creatinine Clearance 3.0 x up-per limit of normal •Serum total bilirubin > 2 ULN except unconjugated hyperbilirubinemia related toMDS. 13.ubjects with = grade-2 neuropathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective of the trial: The goal will be to identify the “safe most successful dose” (sMSD) that is the dose level where the probabilities of success is maximized across the dose levels and the toxicity rate is kept within acceptable boundaries.;Secondary Objective: Secondary objectives of the trial: Response rate (according to IWG 2006 criteria for MDS and Cheson criteria for AML) to the combination of lenalidomide and azacitidine in adult high and int 2 MDS (IPSS) or AML with del 5q[31] . Safety (particularly hematological toxicity) of the combination of Lenalidomide and azacitidine in int-2 and high risk MDS or AML with del 5q [31]. •Duration of response, •Progression to AML, •And overall survival. ;Primary end point(s): Primary end point: In this trial, we will test the combination of escalating doses of Lenalidomide (starting at relatively low dose) and azacitidine in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31 without major toxicity, by comparison with historical results obtained with Lenalidomide alone in the same subset of patients in a phase II study recently conducted by the GFM, and results obtained with Azacitidine alone (AZA 001 Phase III study). | — |
Countries
France
Outcome results
None listed