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Primary MyelofibrosisPhase 1/2NCT01298934

LBH589 (Panobinostat) for the Treatment of Myelofibrosis

A Phase 1/2 study testing LBH589 in people with Primary Myelofibrosis and Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, run by Ronald Hoffman at 1 site in United States.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

LBH589 is an oral drug that targets the myelofibrosis cells in the bone marrow and induces cell death by allowing for the expression of certain suppressed genes that are important in regulating cell survival. Read more about this study

Who is it for?
Ages 18 years and older
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
22 participants
Where
1 siteUnited States
Study dates
Sep 2009to Jul 2015
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

  • Male or female patients aged ≥ 18 years old
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Newly diagnosed MF with intermediate or high risk Lille Scoring System (Hb<10g/dL, WBC <4.0 or >30 X 109/L; risk group 1=intermediate and 2= high), or symptomatic splenomegaly that is >10cm below costal margin.
  • Previously treated MF that are refractory, intolerant or relapsed in disease
  • Patients must meet the following laboratory criteria:
  • ANC ≥ 1.0 x 109/L
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  • Platelets ≥ 60 x 109/L
  • Calculated CrCl ≥ 45 mL/min (MDRD Formula)
  • AST and ALT ≤ 2.5 x ULN
  • Serum bilirubin < 1.5 x ULN
  • Albumin > 3.0 g/dl
  • Serum potassium ≥ LLN
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN,
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • TSH ≤ ULN and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
  • ECOG Performance Status of ≤ 2

Who cannot join

  • Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
  • Peripheral neuropathy > 1
  • 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)
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  • 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 LBH589
  • Patients with diarrhea > CTCAE grade 1
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) 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
  • Concomitant use of CYP3A4 inhibitors
  • 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 chemotherapy within 3 weeks; or radiation therapy to > 30% of marrow-bearing bone within 3 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
  • Patients with an active bleeding tendency or are receiving any treatment with therapeutic doses of sodium warfarin (Coumadin®) or coumadin derivatives. Low doses of Coumadin® (e.g. ≤ 2 mg/day) to maintain line patency (if applicable) is allowed.
  • 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 using an effective method of birth control. WOCBP are defined as sexually mature 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 24hrs of receiving the first dose of study medication.
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • 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.
  • Disease associated with secondary MF such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease or acute leukemia (including M7 disease or acute panmyelosis with MF)
  • Presence of chromosomal translocation t(9:22) or molecular BCR/ABL rearrangement as detected by RT-PCR in bone marrow or peripheral blood.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: A Phase I/II Open Label Study of LBH589, a Novel Histone Deacetylase Inhibitor (HDACi), in Patients With Primary Myelofibrosis (PMF) and Post-polycythemia/Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

LBH589 is an oral drug that targets the myelofibrosis cells in the bone marrow and induces cell death by allowing for the expression of certain suppressed genes that are important in regulating cell survival. Based on laboratory studies, the hypothesis is that this drug will selectively kill the stem cells responsible for causing myelofibrosis and result in reduction in spleen size and ultimately restoration of normal bone marrow function.

Being tested
LBH589
Medical subject headings
Primary Myelofibrosis, Polycythemia Vera

What participants receive

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

  • LBH589Drug

    Also called Panobinostat

    Dose escalation study starting at 20mg by mouth three times a week, given weekly for 24 weeks in the phase I portion of the study.

Study groups in NCT01298934
Study groupRoleWhat they receive
LBH589ExperimentalDose escalation study starting at 20mg by mouth three times a week, given weekly for 24 weeks in the phase I portion of the study.
Receives: Drug: LBH589

What is being measured

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

  1. To assess the safety and tolerability of oral LBH589 in patients with PMF, post-PV/ET MF

    Phase I

    Measured: 28 days

  2. Evaluation of treatment response by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)

    Phase II

    Measured: 6 months

Secondary outcomes (1)

  1. Assess changes in biomarkers

    JAK2V617F allele burden H3/H4 acetylation status peripheral blood CD34+ stem cell burden CXCR4 expression on CD34+ peripheral blood stem cells

    Measured: 6 months

Timeline

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

  1. First posted18 Feb 2011 (estimated)
  2. Study startSep 2009
  3. Primary completionJul 2015 (estimated)
  4. Study completionJul 2015 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01298934
Sponsor's protocol ID
GCO 08-0572
Other IDs
LBH589-JM
Status last verified
Mar 2015
First submitted
16 Feb 2011
Last updated
6 Mar 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LBH589 in people with Primary Myelofibrosis and Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, run by Ronald Hoffman at 1 site in United States.

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 18 inclusion and 28 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 6 Mar 2015. 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 United States. 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?

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 assess the safety and tolerability of oral LBH589 in patients with PMF, post-PV/ET MF (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT01298934.

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 Mar 2015.

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