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Multiple MyelomaPhase 2NCT00445068

Efficacy and Safety of LBH589B in Adult Patients With Multiple Myeloma

A Phase 2 study testing LBH589 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 29 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will evaluate the efficacy and safety of LBH589B in adult patients with multiple myeloma who have received at least two prior therapies and are refractory to their last therapy. Patients must have received in prior therapy either bortezomib or lenalidomide 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
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
29 sitesin 2 countries
Study dates
16 Apr 2007to 25 Dec 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Adults ≥ 18 years old
  • Subjects must have signed the consent form before undergoing any study specific screening procedures and before participation in this study. The subject must be fully informed by the investigator of the nature and potential risks of participation in this study.
  • Patients must have had a diagnosis of symptomatic multiple myeloma (from IMWG see (Kyle et al,2003) meeting all three of the following criteria:
  • Monoclonal immunoglobulin (spike on electrophoresis, or band on immunofixation) on serum or on 24 hour urine.
  • Bone marrow (clonal) plasma cells or plasmacytoma
  • Related organ or tissue impairment (anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity or recurrent infections) (The Kyle et al 2003 definition of symptomatic Myeloma has been adapted based on the new exclusion criteria defined in protocol amendment 1)
Show all 35Show fewer
  • Subjects must have received at least two prior lines of therapy and be refractory to the most recent line of therapy according to the following definitions: Refractory to most recent line of therapy Defined by disease progression during treatment or within 60 - 100 days after the completion of the most recent line of therapy. This includes the development of disease progression during maintenance or consolidation therapy with high dose glucocorticoids, or any other specific MM therapy Sixty days is counted from the point in time when the first response assessment is performed after completion of the last line of therapy. At a maximum, disease progression should be documented within 100 days after the last day of the last dose of any anti-MM therapy, including if last regimen of the most recent line of therapy was Autologous Stem Cell Transplant (ASCT). Stable disease patients also part of the IMWG definition are not eligible for this trial. At study screening, Progressive Disease (PD) will be assessed by comparing screening values or symptoms in reference to the baseline (values or symptoms) of their last line of therapy. Should a patient have experienced an initial response on their last line of therapy, PD should be assessed in reference to the lowest values of the initial confirmed response Minimal Response(MR) / Partial Response (PR) / Complete Response (CR).
  • Disease progression is defined by having one or more of the following:
  • >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.
  • >25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation.
  • >25% increase in plasma cells in a bone marrow aspirate or on bone marrow biopsy, which must also be an absolute increase of at least 10%
  • Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas.
  • Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture).
  • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
  • Subjects must have previously been treated with bortezomib and at least one of the following: lenalidomide or thalidomide
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  • Patients must have the following hematological laboratory values:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (or ≥1.0 x 109/L if the neutropenia is clinically related to progressive myeloma with bone marrow infiltration of > 50% involvement
  • Hemoglobin ≥ 8.0 g/dl
  • Platelets ≥ 75.0 x 109/L (or ≥ 50.0 x 109/L x if the thrombocytopenia is clinically related to progressive myeloma with bone marrow infiltration > 50% involvement
  • Patients must have the following renal function as shown by :
  • Calculated Creatinine Clearance (CrCL) > 30ml/min (Cockcroft and Gault formula)
  • Patients must have adequate liver function as shown by:
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x Upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 x ULN
  • Albumin ≥ 2.5 g/dl
  • Patients must have the following non-hematological laboratory values:
  • Serum potassium ≥ Lower Limit of Normal (LLN),
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN,
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • Normal thyroid function (TSH and free T4) (hypothyroidism correctable with supplements is allowed)
  • Baseline Multiple Uptake Gated Acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate Left Ventricular Ejection Fraction (LVEF) ≥ the lower limit of the institutional normal
  • Patients must be willing and able to undergo bone marrow aspirates as per protocol, with/without bone marrow biopsy according to their center's practice. The bone marrow aspirate /biopsy must be adequate to allow for comparison for the later efficacy response assessments.
  • Patients must have an M component at baseline above a minimum threshold of: 1g/dl (10g/L) for serum M component, or 200mg/24h urine M component.

Who cannot join

  • Prior therapy with an Histone Deacetylase (HDAC) inhibitor for the treatment of Multiple Myeloma (MM)
  • Patients with non-secretory MM
  • Patients who have received allogenic stem cell transplantation < 12 months prior to study
  • Patients who have had prior allogenic stem cell transplantation and show evidence of active graft versus-host disease that requires immunosuppressive therapy
  • Patients with amyloidosis
  • Patients with peripheral neuropathy > grade 2
Show all 30Show fewer
  • 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 Heart Rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
  • Screening Electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec
  • Right bundle branch block + left anterior hemi-block (bi-fascicular block)
  • Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
  • Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF NY) Heart Association class III or IV, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
  • Patients with unresolved diarrhea > CTCAE grade 1.
  • Other concurrent severe and/or uncontrolled medical conditions 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 torsades de pointes if the medications cannot be discontinued or switched to a different medication prior to starting study drug
  • Concomitant use of CYP3A4 inhibitors
  • Patients with an active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin (Coumadin®) or any other anti-vitamin K drug. Low doses of Coumadin® (e.g., ≤ 2 mg/day), or low doses of any other anti-vitamin K drug, for line patency is allowable
  • Patients who have received chemotherapy, radiation therapy or any investigational drugs, bortezomib or other immunomodulatory therapy (e.g., thalidomide, lenalidomide) or immunotherapy ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who have received high-dose corticosteroids as the only component of their most recent line of therapy
  • Patients who have received steroids (e.g., dexamethasone) ≤ 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 subjects receive < 20 mg of prednisone or equivalent as indicated for other medical conditions (and not as maintenance or an anticancer therapy for MM), or up to 100 mg of hydrocortisone as premedication for a administration of certain medications or blood products, while enrolled in this study.
  • Patients whose clinical condition would need valproic acid therapy during study or ≤ 5 days prior to starting drug
  • 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 LBH589
  • 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 current second malignancy or a prior malignancy within the last 5 years except adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • Patients with any significant history of non compliance to medical regimens or unwilling or unable to comply with the protocol or unable to grant reliable informed consent.

Trial locations and contacts

29 sites in 2 countries.

29 sites in 2 countries

United States24 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • Aptium Oncology

    Berkeley, California, 94704

  • Dana Farber

    Boston, Massachusetts, 02115

  • Rush University

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Metrohealth

    Cleveland, Ohio, 44109

  • University of Texas Southwestern

    Dallas, Texas, 75390-9179

  • Rocky Mountain Cancer Center

    Denver, Colorado, 80218

  • City of Hope

    Duarte, California, 91010

  • Duke

    Durham, North Carolina, 27710

  • Hackensack University

    Hackensack, New Jersey, 07456

  • Indiana University

    Indianapolis, Indiana, 46203

  • University of Iowa

    Iowa City, Iowa, 52240-1515

  • Sarah Canon Research Center

    Nashville, Tennessee, 37203

  • Vanderbilt

    Nashville, Tennessee, 37212

  • Christiana Care

    Newark, Delaware, 19718

  • CTRC

    San Antonio, Texas, 78258

  • UCSF

    San Francisco, California, 94143

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Washington University

    St Louis, Missouri, 63110

  • Stanford

    Stanford, California, 94305

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Wake Forest

    Winston-Salem, North Carolina, 27157

Other trials in United States

Germany5 sites

  • Novartis investigative Site

    Berlin

  • Novartis Investigative Site

    Heidelberg

  • Novartis Investigative Site

    Kiel

  • Novartis Investigative Site

    Starnberg

  • Novartis Investigative Site

    Würzburg

Other trials in Germany

About this study

Official title: A Phase II Study Of Oral LBH589 In Adult Patients With Multiple Myeloma Who Have Received At Least Two Prior Lines Of Therapy And Whose Disease Is Refractory To The Most Recent Line Of Therapy

This study will evaluate the efficacy and safety of LBH589B in adult patients with multiple myeloma who have received at least two prior therapies and are refractory to their last therapy. Patients must have received in prior therapy either bortezomib or lenalidomide

Being tested
LBH589
Keywords
Multiple myeloma, adults, LBH589, refractory
Medical subject headings
Multiple Myeloma

What participants receive

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

  • LBH589Drug

    Also called Panobinostat

Study groups in NCT00445068
Study groupRoleWhat they receive
PanobinostatExperimentalParticipants received panobinostat 20 milligrams (mg) orally once daily (OD), three times a week on days: 1, 3 and 5, then 8, 10 and 12, then 15, 17 and 19 of each cycle, as part of a 3-week (21 days) treatment cycle. Participants could continue treatment until disease progression or unacceptable toxicity.
Receives: Drug: LBH589

What is being measured

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

  1. Response Rate (Complete Response(CR) / Partial Response (PR))

    The response (complete response (CR) / partial response (PR)) rate as per Bladé criteria was assessed by the investigator. Response to treatment was evaluated in participants with multiple myeloma (MM) who have received at least two prior lines of therapy and whose disease was refractory to the most recent line of therapy.

    Measured: From Start of the Study up to 57 Weeks approximately.

Secondary outcomes (11)

  1. Overall Response Rate

    Overall response rate is the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (Overall Response (OR) = CR + PR).

    Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: From Start of the Study up to 57 Weeks approximately.

  2. Clinical Benefit Rate

    Clinical benefit rate is defined by the percentage of participants achieving either a confirmed tumor response or stable disease (SD) for at least 24 weeks. Response Criteria in Solid Tumors (RECIST) is a system for measuring tumor shrinkage or progression in terms of the longest dimensions of the tumor on imaging scans such as computerized tomography (CT). A "partial response" requires a decrease of 30% or more, "Progression" requires an increase of at least 20%, and "Stable disease" falls in between these two. All responses have a repeat assessment to confirm the response

    Measured: From Start of the Study up to 57 Weeks approximately.

  3. Duration of Response

    Duration of response is defined as time between time to first documented response (CR/PR) and time to first documented disease progression or death.

    Measured: From Start of the Study up to 57 Weeks approximately.

  4. Time to Response

    Time to response is defined as time between Day 1 cycle 1 and time to first documented response (CR/PR).

    Measured: From Start of the Study up to 57 Weeks approximately.

  5. Progression Free Survival (PFS)

    Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria.

    Measured: From Start of the Study up to 57 Weeks approximately.

  6. Safety and Tolerability

    Adverse Event (AE) are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

    Measured: From Start of the Study up to 57 Weeks approximately.

  7. Time to Peak Concentration (Tmax) of Panobinostat

    Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's pharmacokinetic (PK) profile, then Tmax will be missing for that subject. Tmax will be reported in units of h.

    Measured: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

  8. Maximum Plasma Concentration (Cmax) of Panobinostat

    Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL.

    Measured: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

  9. Area Under the Plasma Concentration (AUC0-24) of Panobinostat

    Area under the curve (AUC) is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours.

    Measured: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

  10. Last Observed Plasma Concentration (Clast) of Panobinostat

    Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast.

    Measured: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

  11. Time of Clast (Tlast) of Panobinostat

    Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h.

    Measured: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Timeline

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

  1. First posted8 Mar 2007 (estimated)
  2. Study start16 Apr 2007
  3. Primary completion19 May 2008
  4. Study completion25 Dec 2009

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00445068
Sponsor's protocol ID
CLBH589B2203
Status last verified
Jun 2021
First submitted
7 Mar 2007
Last updated
14 Jul 2021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LBH589 in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 29 sites in 2 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 35 inclusion and 30 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 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Germany. 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 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?

Yes. Results are posted in the registry (first posted 14 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Response Rate (Complete Response(CR) / Partial Response (PR)) (time frame: From Start of the Study up to 57 Weeks approximately.). 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 NCT00445068.

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 14 Jul 2021.

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