A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q
1. age > ou = 18 years and < 75 years.
2. must understand and voluntarily sign an informed consent form.
3. 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 thalidomide allowed.
6. documented diagnosis of MDS (according to FAB definition, ie. with marrow blasts up
to 30%, or CMML with WBC < 13000/mm3 that meets IPSS criteria for intermediate-2 or
7. with an associated del 5q(the deleted chromosomal region must include 5q),
with or without additional cytogenetic abnormalities.
8. female subjects of childbearing 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 25mIU/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
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 amenorrhea this applies unless the subject commits
to absolute and continuous abstinence confirmed on a monthly basis, to avoid
pregnancy for the duration of study.
the following are effective methods of contraception:
- levonorgestrel-releasing intrauterine system(IUS)
- Medroxyprogesterone acetate depot, tubal sterilization.
- sexual intercourse with a vasectomised male partner only(vasectomised must be
confirmed by two negative semen analyses), ovulation inhibitory
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
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
- She understands the potential consequences of pregnancy and the need to rapidly
consult if there is a risk of pregnancy
9. Male patients must :
- Agree the need for the use of a condom if engaged in sexual activity with a
woman of childbearing potential. during the entire period of treatment, even if
disruption of treatment and during 3 months after end of treatment
- Agree not to conceive during treatment and study drug therapy (including doses
interruptions) and for 3 months after the end of the study drug therapy
- Agree not to donate semen during study drug therapy and for one week after end
of study drug therapy.
- Agree to learn about the procedures for preservation of sperm., before starting
10. 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.
11. Signed informed consent prior to start of any study-specific procedures,
12. Ability to participate to a clinical trial and adhere to study procedures.
- Criteria for women of non-childbearing potential :
A female patient or a female partner of a male patient is considered to have childbearing
potential unless she meets at least one of the following criteria:
- Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer
therapy does not rule out childbearing potential)
- Premature ovarian failure confirmed by a specialist gynaecologist
- Previous bilateral salpingo-oophorectomy, or hysterectomy
- XY genotype, Turner syndrome, uterine agenesis.