Study of Vorinostat Plus Melphalan and Prednisone (Zmp) in Advanced, Refractory Multiple Myeloma Patients
This study has been terminated.
(The Phase I of the study was completed, but Phase 2 has not been activated)
Information provided by (Responsible Party):
Tiziana Marangon, University of Turin, Italy
First received: March 4, 2009
Last updated: May 9, 2016
Last verified: May 2016
The purpose of this study is to determine whether the association of ZMP is safe and provides benefits in patients with relapsed/refractory MM.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients
Primary Outcome Measures:
- The dose limiting toxicity (DLT)of Vorinostat with MP [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- The maximum tolerated dose (MTD) of Vorinostat in association with MP [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- A significant number of PR or higher (>40%) following the proposed ZMP therapy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Duration of Progression Free Survival [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
- Duration of Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Estimated Study Completion Date:
| Primary Completion Date:
||March 2012 (Final data collection date for primary outcome measure)
Combination with Vorinostat, Melphalan and Prednisone
Patients will start induction treatment with a standard dose of MP and escalating doses of Vorinostat:
- Melphalan 0.18 mg/Kg for 4 days; Prednisone 1.5 mg/Kg for 4 days. Each cycle will be repeated every 28 days for a total of 6 courses
- In the first part of the study, the standard oral MP will be combined with escalating doses of Vorinostat.
Level -1 Vorinostat = 100 mg daily on days 1-21 Melphalan = 0.18 mg/kg on days 1 - 4 Prednisone = 1.5 mg/kg on days 1 - 4
Level 0 Vorinostat = 200 mg daily on days 1-21 Melphalan = 0.18 mg/kg on days 1 - 4 Prednisone = 1.5 mg/kg on days 1 - 4
Level +1 Vorinostat = 300 mg daily on days 1-21 Melphalan = 0.18 mg/kg on days 1 - 4 Prednisone = 1.5 mg/kg on days 1 - 4
Level +2 Vorinostat = 400 mg daily on days 1-21 Melphalan = 0.18 mg/kg on days 1 - 4 Prednisone = 1.5 mg/kg on days 1 - 4
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00857324
|Dipartimento Medicina Clinica e Sperimentale
|Padova, Italy, 35128 |
|A.O.U. S. Giovanni Battista
|Torino, Italy, 10126 |
|Policlinico Universitario di Udine
|Udine, Italy, 33100 |
|Azienda Ospedaliera di Verona - Policlinico G.B. Rossi
|Verona, Italy, 37134 |
||Mario Boccadoro, MD
||University of Turin
||Tiziana Marangon, Sponsor, University of Turin, Italy
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 4, 2009
||May 9, 2016
||Italy: Ethics Committee
Keywords provided by University of Turin, Italy:
Refractory or relapsed patients
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 28, 2016
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Blood Protein Disorders
Immune System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating