A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients
- Age ≥ 18 years
- Patient is, in the investigator(s) opinion, willing and able to comply with the
- Patient has given voluntary written informed consent before performance of any study
related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
- Female patient is either post-menopausal for 24 consecutive months or surgically
sterilized or agree to continuous abstinence from heterosexual sexual contact or
willing to use effective contraception for 4 weeks prior to beginning study drug
therapy, during study drug therapy (including dose interruption) and for 4 weeks
after discontinuation of therapy; female patients not pregnant or nursing; female
with a negative pregnancy test.
- Male patient agrees to use an acceptable method for contraception during study drug
therapy (including dose interruption) and for 4 weeks after discontinuation of
- Patient was previously diagnosed with symptomatic MM based on standard criteria, and
has measurable disease.
- Patient is relapsed or refractory after a minimum of 3 weeks from prior therapies
(patients must have recovered from toxicities related to prior therapies).
- Patient has a Karnofsky performance status ≥ 60%.
- Patient has a life-expectancy > 3 months.
- Any serious medical condition, laboratory abnormality, or psychiatric illness or
social situation that would prevent the subject from signing the informed consent
form or limit the compliance with study medications and requirements.
- Pregnant or beast feeding females.
- Use of any other concomitant standard/experimental anti-myeloma drug or therapy.
- Known positive for HIV or active infectious hepatitis, type B or C.
- Known congenital long QT syndrome.
- Ongoing therapy with anti-arrhythmic drugs or other medicinal products which led to
QT prolongation and cumulative high dose of anthracycline.
- Any clinically significant illness that would, in the investigator's opinion,
increase the patient's risk for toxicity. Patients has not plasmacell leukaemia
defined as the presence of more than 20% plasma cells in the peripheral blood and an
absolute plasma cell count of at least 2000/uL.
- Patients has not a currently active malignancy, except non melanoma skin cancer and
carcinoma in situ of the cervix. Patients should not be considered to have a
currently active second malignancy if they have completed therapy for a prior
malignancy and are disease free from prior malignancies for >5 years and are
considered by their physicians to be at less then 30% risk of relapse
- History of allergic reactions related to study drugs.
- Prior exposure to HDACi. Patients exposed to valproic acid could be eligible with a
wash out period of at least 30 days.
- Patients scheduled to undergo autologous or allogenic bone marrow transplant within 4
week of the initiation of Vorinostat administration.