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Multiple MyelomaPhase 1NCT00532389

Safety Study of LBH589 When Given in Combination With Bortezomib in Adult Patients With Multiple Myeloma

A Phase 1 study testing LBH589 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 16 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study comprises of a dose-escalation and dose expansion phase and will determine the maximum tolerated dose of oral Panobinostat on a continuous schedule in adult in combination with bortezomib. Safety, tolerability, PK and PD profile of the combined treatments will be assessed as secondary objectives. 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?
LBH589
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
16 sitesin 6 countries
Study dates
Oct 2007to Oct 2013
Phase
Phase 1
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

  • Patients must have a diagnosis of active multiple myeloma according to the International Myeloma Working Group criteria (IMWG., 2003), and be deemed by the investigator as requiring treatment.
  • Patients must have received at least one prior line of therapy and includes patients whose disease has relapsed as well as relapsed-refractory MM . (Durie et. al., 2006). One prior line of therapy may consist of induction followed by autologous stem cell transplantation.
  • Patients must be suitable (according to their local product information and applicable health authority recommendations) for treatment with BTZ. Note: patients previously treated with BTZ are eligible to participate in the trial.
  • Patients enrolled to dose expansion phase must have measurable M component at entry according to the IMWG Criteria (Durie et al, 2006) including at least one of the following:
  • Serum M-protein by sPEP ≥ 1 g/dL (> 10g/l)
  • For patients with IgA M-protein whose sPEP is not providing sufficiently precise quantification due to confounded migration of M-protein with serum beta globulins, a quantification by nephelometry / turbidometry is permitted and must show serum M-protein ≥ 1 g/dL
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  • Urine M-protein by uPEP ≥ 200 mg/24 h
  • Serum FLC assay: Involved FLC level ≥ 100 mg/L, provided serum FLC ratio is abnormal. (abnormal if FLC ratio is <0.26 or >1.65 )
  • Adults ≥ 18 years old
  • ECOG Performance Status ≤ 2
  • Life expectancy > 12 weeks
  • Patients must have the following laboratory values:
  • ANC ≥ 1.5 x 109/L
  • Platelets ≥ 100x 109/L
  • Calculated CrCl ≥ 30 mL/min (MDRD Formula)
  • AST and ALT ≤ 2.5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN
  • Serum potassium, magnesium, phosphorous, within normal limits (WNL) for institution
  • Total calcium (corrected for serum albumin) or ionized calcium equal to lower normal limits for institution or greater (≥ LLN) but not higher than CTCAE grade 1
  • Note: Potassium, calcium, magnesium, and/or phosphorous supplements may be given to correct values that are < LLN.
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal
  • All patients (dose-escalation and dose-expansion patients) must be willing to undergo a mandatory bone marrow aspirate sampling at baseline (for cytology) and another later in the study if the patient eventually goes on to experience a CR or PR. For patients who join the study at the dose-expansion phase, they must also give consent to have an extra volume of sample taken for exploratory biomarker testing. Potential dose-expansion phase patients who do not consent for this biomarker sample collection will not be eligible to participate in the trial (Note: One extra bone aspirate sample at C2D1 is optional as per the protocol).
  • Able to sign informed consent and to comply with the protocol
  • Patient is able to swallow capsules

Who cannot join

  • Prior exposure to a HDAC inhibitor compound used in the treatment of MM
  • Patients with Refractory MM (i.e. patients refractory to all prior therapies) who under all prior previous lines of therapy have :
  • either never reached a response better than SD
  • or whose disease progressed from any best response while still under therapy
  • or whose disease progressed within 60 days of last dose of therapy
  • Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease or of graft-versus-host disease that requires immunosuppressive therapy.
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  • Patient has grade 1 peripheral neuropathy with pain or grade ≥ 2 peripheral neuropathy on clinical examination within 14 days before first study treatment
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • Patients with congenital long QT syndrome
  • History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment)
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
  • Screening ECG with a QTc > 450 msec
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
  • Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of GI function or GI disease that may significantly alter the absorption of PAN
  • Patient has unresolved diarrhea ≥ CTCAE grade 2
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction ) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Patients who need valproic acid for any medical condition during the study or within 5 days prior to the first PAN treatment.
  • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (which ever is longer) and who have not recovered from side effects of those therapies.
  • Patients who have received either immunotherapy within ≤ 8 weeks; chemotherapy within ≤ 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within ≤ 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
  • Patients who have received steroids (e.g. Dex) ≤ 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if patients receive < 10 mg of prednisone or equivalent as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products while enrolled in this study.
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)not willing to use a double method of contraception during the study and for 3 months after treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of oral PAN
  • Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and for 3 months after treatment. One of these methods of contraception must be a condom
  • Patients with a prior malignancy with in the last 3 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.
  • Patients who have shown intolerance to BTZ or to Dex or components of these drugs or has any contraindication to one or the other drug, following locally applicable prescribing information
  • Other protocol defined inclusion/exclusion criteria may apply

Trial locations and contacts

16 sites in 6 countries.

16 sites in 6 countries

Germany5 sites

  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    München, 80336

  • Novartis Investigative Site

    Würzburg, 97070

Other trials in Germany

United States4 sites

  • Dana Farber Cancer Institute Clinical Research Coordinator

    Boston, Massachusetts, 02115

  • Hackensack University Medical Center Multiple Myeloma Division

    Hackensack, New Jersey, 07601

  • Innovative Medical Research of South Florida Dept.ofInnovativeMedResearch

    Miami Shores, Florida, 33138

  • Swedish Medical Center Dept.ofSwedishMedicalCtr.

    Seattle, Washington

Other trials in United States

Canada2 sites

  • Novartis Investigative Site

    Montreal, Quebec, H1T 2M4

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Italy2 sites

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Torino, TO, 10126

Other trials in Italy

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    Salamanca, Castille and León, 37007

Other trials in Spain

Australia1 site

  • Novartis Investigative Site

    Canberra, Australian Capital Territory, 2606

Other trials in Australia

About this study

Official title: A Phase Ib, Multi-center, Open-label, Dose-escalation Study of Oral LBH589 When Administered in Combination With Bortezomib in Adult Patients With Multiple Myeloma

This study comprises of a dose-escalation and dose expansion phase and will determine the maximum tolerated dose of oral Panobinostat on a continuous schedule in adult in combination with bortezomib. Safety, tolerability, PK and PD profile of the combined treatments will be assessed as secondary objectives. Dose expansion phase will explore in a non continuous Panobinostat schedule with bortezomib and dexamethasone, safety and tolerability and PK profile of Panobinostat and Bortezomib with and without Dexamethasone

Being tested
LBH589
Keywords
Myeloma, Multiple Myeloma, Bortezomib, LBH589, Combination
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

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

  • LBH589Drug

Study groups in NCT00532389
Study groupRoleWhat they receive
Panobinostat (LBH589)ExperimentalNot described
Receives: Drug: LBH589

What is being measured

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

  1. To determine the MTD of panobinostat with bortezomib

    Measured: throughout the study

Secondary outcomes (3)

  1. The safety and tolerability of the study continuous Panobinostat treatment in dose escalation phase and non continuous schedule of panobinostat in dose expansion phase

    Measured: throughtout the study

  2. To characterize the PK profile of bortezomib; the PK profile of panobinostat with and without bortezomib; the PK profile of bortezomib and panobinostat with and without dexamethasone

    Measured: cycle 1 & cycle 2

  3. To assess the preliminary efficacy of the study treatment

    Measured: throughout the study

Timeline

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

  1. First posted20 Sep 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionOct 2013
  4. Study completionOct 2013

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00532389
Sponsor's protocol ID
CLBH589B2207
Other IDs
2006-006638-16
Status last verified
Oct 2014
First submitted
18 Sep 2007
Last updated
19 Dec 2020
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LBH589 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 16 sites in 6 countries.

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 24 inclusion and 31 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: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Germany, United States, Canada, Italy, Spain and 1 more country. 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 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To determine the MTD of panobinostat with bortezomib (time frame: throughout the study). 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 NCT00532389.

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 19 Dec 2020.

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