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Waldenstrom's MacroglobulinemiaPhase 2NCT00936611

LBH589 in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia

A Phase 2 study testing LBH589 in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites in United States.

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

The purpose of this research study is to assess the overall response rate of LBH589 in patients with relapsed or refractory Waldenstrom's Macroglobulinemia. LBH589 is a newly discovered compound that has killed Waldenstrom cells in laboratory studies, however, it is not known if LBH589 will show the same activity in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom's Macroglobulinemia
What is being tested?
LBH589
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
2 sitesUnited States
Study dates
Jul 2009to Nov 2012
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

  • Male or female patients aged 18 years or older
  • Must have received prior therapy for their WM, any number of prior therapies is allowed
  • Must have symptomatic relapsed or refractory WM
  • Measurable monoclonal IgM protein in the blood and presence of lymphoplasmacytic cells in the bone marrow during any previous bone marrow
  • Laboratory values as described in the protocol
  • Clinically euthyroid
  • ECOG Performance Status of 2 or less

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 CTCAE grade 2 or higher
  • Impaired cardiac function or clinically significant cardiac diseases
  • Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
  • Diarrhea > CTCAE grade 1
Show all 18Show fewer
  • Other concurrent severe and/or uncontrolled medical conditions 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 have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
  • Patients who have received chemotherapy or rituximab within 3 weeks or less; or radiation therapy to > 30% of marrow-bearing bone within 2 weeks or less prior to starting study treatment; or who have not yet recovered from side effects of such therapies
  • Patients who have received corticosteroids 2 weeks or less prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than than Waldenstrom's Macroglobulinemia
  • Patients with active bleeding tendency or receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin to maintain line patency is allowed
  • Patients who have undergone major surgery 4 weeks or less 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 not using an effective method of birth control
  • Male patients whose sexual partners are women of childbearing potential not using effective methods of birth control
  • Patients with prior malignancy within 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 a 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Rocky Mountain Cancer Centers

    Denver, Colorado, 80220

Other trials in United States

About this study

Official title: Phase II Trial of LBH589 (Panobinostat) in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia

The purpose of this research study is to assess the overall response rate of LBH589 in patients with relapsed or refractory Waldenstrom's Macroglobulinemia. LBH589 is a newly discovered compound that has killed Waldenstrom cells in laboratory studies, however, it is not known if LBH589 will show the same activity in people with Waldenstrom's Macroglobulinemia. This drug has been used in research for the treatment of other types of cancer, such as multiple myeloma.

Read the detailed description

This phase II study is designed to assess the toxicity profile and the proportion of overall response in patients with relapsed or refractory WM. This will study the effect of single agent LBH589 on response in these patients. Efficacy measures will include both objective clinical measurements and investigator-reported outcomes. Response and time to event analyses will follow the criteria set forth in the International Waldenstrom consortium recommendations. Prior to the start of the study, investigators will assess disease and perform a CT scan of the chest, abdomen and pelvis.

Response will be assessed after 2 cycles. If patients have stable disease or response, then they will continue on therapy until progression or unacceptable toxicity, being assessed every cycle until the sixth cycle and then every 3 months. Patients who show progression after 2 cycles will come off therapy and undergo event monitoring every 3 months. All responses will be assessed by M-protein quantification and immunofixation from serum and IgM monoclonal protein level. In addition, BM biopsies will be done at baseline, at the end of cycle 6 and at the end of all therapy. The protocol was amended because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.

Being tested
LBH589
Keywords
LBH589, WM, panobinostat, relapsed, waldenstrom, macroglobulinemia
Medical subject headings
Waldenstrom Macroglobulinemia, Recurrence

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 NCT00936611
Study groupRoleWhat they receive
LBH589Experimental30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: * 25 mg, 20 mg three times a week every week * Or 20 mg three times a week every other week. No dose re-escalation was allowed. * The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose.
Receives: Drug: LBH589

What is being measured

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

  1. Overall Response Rate

    Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment.

    CR

    • Disappearance of monoclonal protein by immunofixation
    • No histologic evidence of bone marrow involvement
    • Resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM.
    • Second immunofixation required for confirmation.

    VGPR

    -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis.

    PR

    • At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan.
    • No new symptoms or signs of active disease.

    MR

    • At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis.
    • No new symptoms or signs of active disease.

    Measured: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.

Secondary outcomes (5)

  1. Median Progression Free Survival

    Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.

    Measured: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

  2. Median Time to Progression

    Time to progression (TTP) is defined as the time from start of treatment to progression. Patients who have not progressed are censored at the date the patient is last known to be progression free.

    Measured: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

  3. Median Duration of Response

    Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression Patients who have died for any cause or are alive without progression are censored at the date the patient is last know to be progression-free.

    Duration of response DR is defined as the time from the date of first response after treatment to the date of disease progression or death for any cause. Patients who are alive without progression are censored at the date the patient is last know to be progression-free.

    Measured: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles and then every 3 months. If taken off treatment at cycle 2 for disease progression, assessed every 3 months. The median (range) follow up from treatment start is 7.7 month (0.9 - 29.7).

  4. Number of Participants With Grade 3 and 4 Treatment-Related Thrombocytopenia

    Grade 3 thrombocytopenia is defined as having 25,000-50,000 /uL platelets

    Grade 4 thrombocytopenia is defined as having < 25,000 /uL platelets

    Measured: Assessed after 2nd cycle, every subsequent cycle for 6 cycles and then every 3 months. Once off-treatment, adverse events will be assessed for 30 days. The median (range) number of completed cycles of therapy was 5 (0- 32). Therefore, up to ~33 months.

  5. Acetylated Histone H3 and Overall Response Association

    Acetylated-histone-H3 levels were obtained through bone marrow biopsies and measured using established methods. This analysis aimed to analyze the association between overall response and percent change of acetylated histone h3 in samples using a paired t-test.

    Measured: Bone marrow biopsies were obtained at the start of treatment (baseline) and after the 6th cycle.

Timeline

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

  1. First posted10 Jul 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionSep 2011
  4. Study completionNov 2012

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00936611
Sponsor's protocol ID
09-071
Other IDs
CLBH589CUS56T
Status last verified
Jan 2021
First submitted
9 Jul 2009
Last updated
28 Jan 2021
Data monitoring committee
Yes

Publications

  • Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. doi: 10.1182/blood-2012-06-439307. Epub 2013 Jan 3.

    PubMed 23287861

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LBH589 in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites 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 7 inclusion and 18 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 28 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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 28 Jan 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?

Overall Response Rate (time frame: Assessed after 2nd cycle and then every subsequent cycle for 6 cycles. The median number of completed cycles of therapy was 5 (0- 32). As such observed up to ~32 months.). 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 NCT00936611, 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 28 Jan 2021.

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