Multiple MyelomaPhase 1/2NCT00857324
Study of Vorinostat Plus Melphalan and Prednisone (Zmp) in Advanced, Refractory Multiple Myeloma Patients
A Phase 1/2 study testing Vorinostat in people with Multiple Myeloma, run by Tiziana Marangon at 4 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesItaly
- Study dates
- Mar 2009to May 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Dipartimento Medicina Clinica e Sperimentale
Padova, 35128
A.O.U. S. Giovanni Battista
Torino, 10126
Policlinico Universitario di Udine
Udine, 33100
Azienda Ospedaliera di Verona - Policlinico G.B. Rossi
Verona, 37134
About this study
Official title: A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients
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
- Being tested
- Vorinostat
- Keywords
- Refractory or relapsed patients, dose-finding, Vorinostat
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
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
| Study group | Role | What they receive |
|---|---|---|
| ZMP | Experimental | Combination with Vorinostat, Melphalan and Prednisone Receives: Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
The dose limiting toxicity (DLT)of Vorinostat with MP
Measured: one year
The maximum tolerated dose (MTD) of Vorinostat in association with MP
Measured: 1 year
A significant number of PR or higher (>40%) following the proposed ZMP therapy
Measured: 1 year
Secondary outcomes (2)
Duration of Progression Free Survival
Measured: 5 Years
Duration of Overall Survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionMar 2012
- Study completionMay 2017
Why it stopped: The Phase I of the study was completed, but Phase 2 has not been activated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tiziana Marangon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tiziana Marangon, University of Turin, Italy
- Investigators
- Mario Boccadoro, MD, Principal investigator, University of Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857324
- Sponsor's protocol ID
- ZMP-1
- Other IDs
- 2008-000646-32, 2008
- Status last verified
- Sep 2017
- First submitted
- 4 Mar 2009
- Last updated
- 6 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multi-Center, Open Label Study of Vorinostat Plus Melphalan and Prednisone (ZMP) in Advanced, Refractory Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT00857324
- Acronym / sponsor ID
- ZMP-1
- Conditions
- Multiple Myeloma
- Keywords
- Refractory or relapsed patients, dose-finding, Vorinostat
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Phase I of the study was completed, but Phase 2 has not been activated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Tiziana MarangonUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the association of ZMP is safe and provides benefits in patients with relapsed/refractory MM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZMP | Experimental | Drug: VorinostatCombination with Vorinostat, Melphalan and Prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatPatients 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 | Drug | ZMP |
Primary outcome
The dose limiting toxicity (DLT)of Vorinostat with MP
Time frame: one year
The maximum tolerated dose (MTD) of Vorinostat in association with MP
Time frame: 1 year
A significant number of PR or higher (>40%) following the proposed ZMP therapy
Time frame: 1 year
2 secondary outcomes
Duration of Progression Free Survival
Time frame: 5 Years
Duration of Overall Survival
Time frame: 5 years
Results and safety
The study was stopped early (reason given: The Phase I of the study was completed, but Phase 2 has not been activated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Boccadoro, MD principal investigator
University of Turin, Italy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vorinostat in people with Multiple Myeloma, run by Tiziana Marangon at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The Phase I of the study was completed, but Phase 2 has not been activated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The dose limiting toxicity (DLT)of Vorinostat with MP (time frame: one year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2017.