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Multiple MyelomaPhase 1/2NCT00431990

A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma

A Phase 1/2 study testing depsipeptide, bortezomib and dexamethasone in people with Multiple Myeloma, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of the first phase of the study is to determine whether, and at what dose, depsipeptide, bortezomib and dexamethasone can be safely administered to patients with Multiple Myeloma. 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?
depsipeptide, bortezomib and dexamethasone
Type of treatment
Injection or infusion
How many people
40 participants
Where
1 siteAustralia
Study dates
Nov 2006to Jan 2012
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

  • Patient was previously diagnosed with multiple myeloma based on standard criteria treated with at least one, but less than 4 lines of therapy, and currently requires further treatment because of relapse from CR or PD.
  • Patient previously treated with bortezomib will be included in the study, if the duration of response was >6mths from the completion of therapy.
  • Patient's age is > 18 yrs
  • Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
  • Patient has given voluntary written informed consent.
  • Female patients of child-bearing potential and male patients with female partners of child-bearing potential, one of whom has not undergone surgical sterilisation must agree to use 2 simultaneous methods of contraception. For female patients, a negative pregnancy test is to be performed within 7 days prior to administration of study drugs.
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  • Patient has measurable disease.
  • serum monoclonal protein (SEP) > 5 g/L
  • serum-free light chains (SFLC) > 100 mg/L
  • urine-free light chains (UFLC) > 200 mg/24hr
  • measurable soft tissue (not bone) plasmacytoma (STPC)
  • Patient has a Karnofsky performance status ≥80%.
  • Patient has a life-expectancy >3 months.
  • Patient has the following laboratory values within 14 days before study drug administration:
  • Platelet count ≥50 × 109/L without transfusion support within 7 days
  • Hemoglobin ≥75 g/L without transfusion support within 7 days
  • Absolute neutrophil count (ANC) ≥0.75 × 109/L without the use of growth factors.
  • Corrected serum calcium <14 mg/dL (3.5 mmol/L).
  • Serum potassium ≥ 4.0 mmol/L and serum magnesium ≥ 0.85 mmol/L (electrolytes can be corrected with supplementation. See section 9.7).
  • Aspartate transaminase (AST): ≤2.5 × the upper limit of normal (ULN).
  • Alanine transaminase (ALT): ≤2.5 × the ULN.
  • Total bilirubin: ≤1.5 × the ULN.
  • Calculated or measured creatinine clearance: ≥20 mL/minute.

Who cannot join

  • Prior severe allergic reactions to bortezomib (Velcade), romidepsin, boron or mannitol
  • Neuropathy > Grade 3 or Neuropathy of Grade 2 with pain > Grade 1 by NCI-CTCAE criteria (v3.0).
  • Patients with the following cardiac risk factors will be excluded from the study (as per the previous NCI trials):
  • Congenital long QT syndrome
  • QTc interval > 480 milliseconds
  • Patients who have had a myocardial infarction within 12 months of study entry.
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  • Patients who have active coronary artery disease, e.g. angina as defined by Canadian Class II-IV (Appendix 3).
  • Patients with an ECG showing evidence of cardiac ischemia (ST depression of ≥ 2 mm).
  • Patients with congestive heart failure that meets NYHA Class II to IV definitions (Appendix 4) and/or ejection fraction < 45% by MUGA scan or < 50% by echocardiogram and/or MRI.
  • Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD).
  • Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above).
  • Patients with uncontrolled hypertension, i.e. SBP ≥ 160 mm Hg or DBP ≥ 95 mm Hg.
  • Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are excluded from study.
  • Patients with Mobitz II second degree heart block, that do not have a pacemaker.
  • Note: Patients with other cardiac disease may be excluded at the discretion of the principal investigator following consultation with cardiologist.
  • Pregnancy in female patients

Trial locations and contacts

1 site in 1 country.

Joanne Dean contact

613 9656 1111 ext. 1809

Joanne.Dean@petermac.org

Sam Ruell contact

613 9656 1111 ext. 1698

Sam.Ruell@petermac.org

Australia1 site, 1 recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 8006

    Alvin Milner

    Recruiting

Other trials in Australia

About this study

The purpose of the first phase of the study is to determine whether, and at what dose, depsipeptide, bortezomib and dexamethasone can be safely administered to patients with Multiple Myeloma. The second phase of the study will establish whether depsipeptide, bortezomib and dexamethasone is effective in the treatment of patients with multiple myeloma. The study will also examine the role of maintenance therapy with depsipeptide.

Read the detailed description

Several groups have explored the possible synergistic interactions between proteasome and HDAC inhibitors in malignant hematopoietic cells. Bortezomib and HDACIs synergistically induce apoptosis, mitochondrial injury (via BAX), ROS generation and oxidative injury in human leukemia and myeloma cells.

In view of this evidence, we are proposing a trial to examine the clinical effects of combined romidepsin and bortezomib in patients with relapsed/refractory MM. However, there are currently no data as to whether these drugs are safe to administer in combination or at what dose toxicity they may become unacceptable.

Trial Design Open label, single centre, single arm, phase I/II dose escalation trial of bortezomib-dexamethasone with the addition of romidepsin followed by maintenance therapy until disease progression.

Primary objective:

  • To determine the maximum tolerated dose (MTD) of romidepsin administered with Bortezomib in patients with relapsed multiple myeloma by the assessment of adverse events and abnormal laboratory values.

Primary endpoint:

  • Toxicity evaluation at each of four dose levels presented in the dose-escalation schedule

Secondary objective:

  • To determine the efficacy of this combination at the MTD in terms of (i) overall response, (ii) time to progression and (iii) overall survival

Secondary endpoints:

  • Overall response (OR), defined as the best response on treatment based on M Protein response criteria with CR documented to EMBT standard and in conjunction with soft tissue plasmacytomas response criteria and corrected serum calcium level.
  • Time to progression (TTP), defined as the time from commencement of treatment to the date of first evidence of progressive disease.
  • Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause
Being tested
depsipeptide, bortezomib, dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • depsipeptideDrug

    Also called Romidepsin

    Cohort 1. Dose escalation, IV, Weeklyx3 in a 4week cycle. Cohort 2A. 12mg/m2, IV, Weeklyx3 in a 4week cycle. Cohort 2B. 12mg/m2, IV, Weeklyx2 in a 3week cycle.

  • bortezomibDrug

    Also called Velcade

    Cohort 1 and 2A. 3.5mg/m2, IV, day 1, 4, 8, 11 in 28 day cycle. Cohort 2B. 3.5mg/m2, IV, day 1, 4, 8, 11 in 21 day cycle

  • dexamethasoneDrug

    20mg for 2 days with each dose of bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity

    Measured: Until progression

Secondary outcomes (3)

  1. Overall response

    Measured: Until progression

  2. Time to progression

    Measured: Until progression

  3. Overall survival

    Measured: Until progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2007 (estimated)
  2. Study startNov 2006
  3. Primary completionDec 2011 (estimated)
  4. Study completionJan 2012 (estimated)

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00431990
Sponsor's protocol ID
06/34
Status last verified
Aug 2011
First submitted
4 Feb 2007
Last updated
12 Aug 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • Harrison SJ, Quach H, Link E, Seymour JF, Ritchie DS, Ruell S, Dean J, Januszewicz H, Johnstone R, Neeson P, Dickinson M, Nichols J, Prince HM. A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma. Blood. 2011 Dec 8;118(24):6274-83. doi: 10.1182/blood-2011-03-339879. Epub 2011 Sep 12.

    PubMed 21911830

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing depsipeptide, bortezomib and dexamethasone in people with Multiple Myeloma, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.

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 23 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 12 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Joanne Dean (613 9656 1111 ext. 1809, Joanne.Dean@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity (time frame: Until progression). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00431990, which also lists 1 linked publication.

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 12 Aug 2011.

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