Clinical trial NCT00857324: Study of Vorinostat Plus Melphalan and Prednisone (Zmp) in Advanced, Refractory Multiple Myeloma Patients
Official title: A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Refractory or relapsed patients
dose-finding
Vorinostat
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2009-03-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the association of ZMP is safe and provides benefits in patients with relapsed/refractory MM.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
* 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* 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 Vorinostat therapy.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The dose limiting toxicity (DLT)of Vorinostat with MP
timeFrame: one year
measure: The maximum tolerated dose (MTD) of Vorinostat in association with MP
timeFrame: 1 year
measure: A significant number of PR or higher (>40%) following the proposed ZMP therapy
timeFrame: 1 year
Secondary outcomes:
measure: Duration of Progression Free Survival
timeFrame: 5 Years
measure: Duration of Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Dipartimento Medicina Clinica e Sperimentale
city: Torino
country: Italy
facility: A.O.U. S. Giovanni Battista
city: Udine
country: Italy
facility: Policlinico Universitario di Udine
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona - Policlinico G.B. Rossi
Study officials:
affiliation: University of Turin, Italy
name: Mario Boccadoro, MD
role: PRINCIPAL_INVESTIGATOR
References: