Study of Vorinostat Plus Melphalan and Prednisone (Zmp) in Advanced, Refractory Multiple Myeloma Patients

NCT00857324 | Terminated Phase 1 DMC

• 2 other identifiers: ZMP-12008-000646-32
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

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.

Conditions

Multiple Myeloma

Keywords

Refractory or relapsed patients; dose-finding; Vorinostat

Outcome Measures

Primary Outcomes (3)

• The dose limiting toxicity (DLT)of Vorinostat with MP

  one year

• The maximum tolerated dose (MTD) of Vorinostat in association with MP

  1 year

• A significant number of PR or higher (>40%) following the proposed ZMP therapy

  1 year

Secondary Outcomes (2)

• Duration of Progression Free Survival

  5 Years

• Duration of Overall Survival

  5 years

Study Arms (1)

ZMP

EXPERIMENTAL

Combination with Vorinostat, Melphalan and Prednisone

Drug: Vorinostat

Interventions

Vorinostat DRUG

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

ZMP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tiziana Marangon: lead

Study Sites (4)

Dipartimento Medicina Clinica e Sperimentale

Padua, 35128, Italy

Location

A.O.U. S. Giovanni Battista

Torino, 10126, Italy

Location

Policlinico Universitario di Udine

Udine, 33100, Italy

Location

Azienda Ospedaliera di Verona - Policlinico G.B. Rossi

Verona, 37134, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Mario Boccadoro, MD

  University of Turin, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor

Study Record Dates

• First Submitted: March 4, 2009
• First Posted: March 6, 2009
• Study Start: March 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: May 1, 2017
• Last Updated: September 6, 2017

Record last verified: 2017-09

Locations

IT (4)