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)
Sponsor:
Information provided by (Responsible Party):
Tiziana Marangon, University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT00857324
First received: March 4, 2009
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
Drug: Vorinostat
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

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 ]

Enrollment: 18
Study Start Date: March 2009
Estimated Study Completion Date: March 2014
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZMP
Combination with Vorinostat, Melphalan and Prednisone
Drug: Vorinostat

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


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857324

Locations
Italy
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
Sponsors and Collaborators
Tiziana Marangon
Investigators
Principal Investigator: Mario Boccadoro, MD University of Turin
  More Information

No publications provided

Responsible Party: Tiziana Marangon, Sponsor, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT00857324     History of Changes
Other Study ID Numbers: ZMP-1, 2008-000646-32
Study First Received: March 4, 2009
Last Updated: December 10, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by University of Turin, Italy:
Refractory or relapsed patients
dose-finding
Vorinostat

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Vorinostat
Melphalan
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014