A phase ii study of the efficacy and safety of lenalidomide combined to escalating doses of chemotherapy in intermediate-2-or high risk MDS and AML with del 5 q31 - GFM-chimio-Rev-08
- Conditions
- Myelodysplastic Syndrome(MDS) / Acute Myeloid Leukemia(AML)MedDRA version: 9.1Level: LLTClassification code 10028533Term: Myelodysplastic syndrome
- Registration Number
- EUCTR2008-006032-36-FR
- Lead Sponsor
- Groupe Francophone des Myélodysplasies (GFM)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion criteria
1.Age = 18 years
2.Must understand and voluntarily sign an informed consent form
3.Must be able to adhere to the study visit schedule and other protocol requirements
4.No contra indication to anthracycline based chemotherapy
5.Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, or AML with an associated del 5q[31] (the deleted chromosomal region must include 5q[31]), with or without additional cytogenetic abnormalities
6.Female subjects of childbearing potential must:
-Understand that the study medication could have a potential teratogenic risk
- Agree to use, and be able to comply with, effective contraception* without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception.
*Implant, Levonorgestrel-releasing intrauterine system (IUS) (prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection) , Medroxyprogesterone acetate depot, Tubal sterilization, Ovulation inhibitory progesterone-only pills (i.e., desogestrel), Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses.
* Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.
- Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days from the start of study medication 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.
- 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 tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
7.Male subjects must
- Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
-Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
8.All subjects must
-Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
- Agree not to share study medication with another person and to return all unused study drug to the investigator
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
1.Pregnant or lactating females.
2.Contra indication to anthracycline based chemotherapy.
3.Proliferative (WBC = 13,000/mL) CMML.
4.Prior = grade-2 NCI CTCAE (v 3.0) allergic reaction to thalidomide.
5.Prior desquamating (blistering) rash while taking thalidomide.
6.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.
7.Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days .
8.Less than 6 months since prior allogeneic bone marrow transplantation.
9.Less than 3 months since prior autologous bone marrow or stem cell transplantation.
10.Recombinant human erythropoietin (rHuEPO) therapy received within 28 days.
11.Known HIV-1 positivity.
12.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.
13.Creatinine Clearance< 50 ml/min
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: In this trial, we will test the combination of escalating doses of chemotherapy (starting at relatively low dose) with lenalidomide in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will further increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31, without major toxicity in comparison to historical results obtained with chemotherapy alone in the same subset of patients ;Secondary Objective: Secondary objectives of the trial: will be duration of response, progression to AML, survival and safety of the combination of lenalidomide and chemotherapy.;Primary end point(s): The primary endpoint : will be response (CR, mCR and Cri, according to IWG criteria for AML and IWG 2006 criteria for MDS) to the combination of lenalidomide and chemotherapy in adult high and int 2 MDS (IPSS) or AML with deletion 5q[31]
- Secondary Outcome Measures
Name Time Method