Phase II Trial of LBH589 (Panobinostat) in Relapsed or Relapsed and Refractory Waldenstrom's Macroglobulinemia
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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