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A Phase II Study of the Histone Deacetylase (HDAC) Inhibitor LBH589 (Panobinostat) in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

Phase 2
18 Years
Open (Enrolling)
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Peripheral T-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia

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Trial Information

A Phase II Study of the Histone Deacetylase (HDAC) Inhibitor LBH589 (Panobinostat) in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES: I. To evaluate the proportion of confirmed response of LBH589 in
patients with relapsed or refractory non-Hodgkin lymphoma. SECONDARY OBJECTIVES: I. To
describe the toxicities associated with LBH589 in patients with NHL. II. To evaluate overall
survival, progression-free survival, and duration of response in patients treated with
LBH589. TERTIARY OBJECTIVES: I. To evaluate the pharmacokinetics of LBH589. II. To assess
the correlation between clinical (toxicity and/or tumor response or activity) effects with
the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative
laboratory) results. OUTLINE: Patients receive oral panobinostat 3 times weekly. Treatment
repeats every 28 days for up to 12 courses in the absence of disease progression or
unacceptable toxicity. After completion of study treatment, patients are followed up every
6 months for up to 2 years.

Inclusion Criteria

Inclusion Criteria

- Biopsy-proven relapsed or refractory non-Hodgkin lymphoma requiring treatment, who
have failed, unable to tolerate, or refused other available active therapies;
patients should not have other treatment options considered curative (NOTE: for
patients with lymphoma without CNS involvement, a re-biopsy is necessary unless the
patient has had a previous biopsy =< 6 months prior to treatment on this protocol if
there has been no intervening treatment; patients with biopsy-proven CNS lymphoma at
any time are not required to have a rebiopsy to be eligible for this study); NOTE:
relapsed NHL is defined as NHL that relapses after at least one prior therapy and
does not have available curative therapy; refractory NHL is defined as NHL that has
progressed or not responded to most recent therapy and has had at least one prior
therapy and have no available curative therapies

- Measurable disease by CT or MRI or the CT portion of the PET/CT: must have at least
one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x
10^9/L; skin lesions can be used if the area is >= 2 cm in at least one diameter and
photographed with a ruler

- The following disease types are eligible: transformed lymphomas: diffuse large B cell
lymphoma, mantle cell lymphoma, follicular lymphoma grade III; precursor B
lymphoblastic leukemia/lymphoma; mediastinal (thymic) large B-cell lymphoma; Burkitt
lymphoma/leukemia; precursor T-lymphoblastic leukemia/lymphoma; primary cutaneous
anaplastic large cell lymphoma; anaplastic large cell lymphoma - primary systemic
type; small lymphocytic lymphoma/chronic lymphocytic leukemia; follicular lymphoma,
grades 1, 2; extranodal marginal zone B-cell lymphoma of MALT type; nodal marginal
zone B-cell lymphoma; splenic marginal zone B-cell lymphoma; peripheral T cell
lymphoma, unspecified; anaplastic large cell lymphoma (T and null cell type);
lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); CNS lymphoma; post
transplant lymphoproliferative disorders; mycosis fungoides/Sezary syndrome; primary
effusion lymphoma; blastic NK-cell lymphoma; adult T-cell leukemia/lymphoma;
extranodal NK/T-cell lymphoma, nasal type; enteropathy-type T-cell lymphoma;
hepatosplenic T-cell lymphoma; subcutaneous panniculitis-like T-cell lymphoma;
angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma - primary
cutaneous type

- For lymphoplasmacytic lymphoma patients without measurable lymphadenopathy,
measurable disease can be defined by both of the following criteria: bone marrow
lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets,
lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy and
quantitative IgM monoclonal protein > 1,000 mg/dL

- ANC >= 1000/uL

- Hgb >= 9 g/dl

- PLT >= 75,000/uL

- Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x
ULN the direct bilirubin must be normal

- AST =< 3 x ULN

- Albumin > 3.0 g/dl

- Creatinine =< 2.5 x ULN

- Serum potassium, magnesium and phosphorus >= LLN and =< 1.2 x ULN

- Total serum calcium [corrected for serum albumin] or ionized calcium >= LLN

- Clinically euthyroid; 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

- Ability to understand and the willingness to sign a written informed consent document

- Willingness to return to Mayo Clinic

- Life expectancy >= 12 weeks

- Willingness to provide blood and tissues samples for research studies as required by
the protocol

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- ECOG performance status (PS) 0, 1 or 2

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 panobinostat treatment

- Candidate for known standard therapy for the patient's disease that is potentially

- Uncontrolled infection requiring ongoing antibiotics

- Any prior therapy for lymphoma within the previous 2 weeks for standard treatments
and within 4 weeks for experimental therapies unless the patient has recovered from
the nadir of the previous treatment to a level that meets the inclusion criteria

- Receiving corticosteroids > 20mg of prednisone per day (or equivalent)

- Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy
regardless of interval since last treatment

- 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 study PI prior to

- Any history of ventricular fibrillation or torsade de pointes

- Bradycardia defined as HR < 50 bpm; patients with pacemakers are eligible if HR >= 50

- Screening ECG with a QTcFredericia (QTcF) > 450 msec

- Right bundle branch block + left anterior hemiblock (bifascicular block)

- Patients with myocardial infarction or unstable angina =< 6 months prior registration

- 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)

- Pregnant women or women of reproductive ability who are unwilling to use effective
contraception during the study and for 3 months after stopping treatment

- Nursing women

- Men who are unwilling to use a condom (even if they have undergone a prior vasectomy)
while having intercourse with any woman, while taking the drug and for 3 months after
stopping treatment

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-FDA-approved indication and in the
context of a research investigation); patients should have recovered from any
immunotherapy, chemotherapy, or radiation therapy related toxicities

- Known positivity for human immunodeficiency virus (HIV) or hepatitis C with
uncontrolled disease; baseline testing for HIV and hepatitis C is not required

- Active other malignancy requiring treatment that would interfere with the assessments
of response of the lymphoma to protocol treatment

- Inability to swallow or impairment of gastrointestinal function or gastrointestinal
disease that may significantly alter the absorption of the drugs (e.g. ulcerative
disease, uncontrolled nausea, vomiting, diarrhea > CTCAE Grade 2, malabsorption
syndrome or small bowel resection) that would preclude use of oral medications

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months

- Any severe and/or uncontrolled medical conditions or other conditions that, in the
treating physician's opinion, could adversely impact their ability to participate in
the study; patients on chronic oxygen therapy, those with liver disease such as
cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled
infections will be excluded

- Concomitant use of strong or moderate CYP3A4 inhibitors

- 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

- Active bleeding tendency. NOTE: Patients on therapeutic anticoagulation should be
monitored carefully to maintain therapeutic level of anticoagulation to avoid
increased risk of bleeding due to concurrent drug induced thrombocytopenia. It is
suggested that patients who require anticoagulation therapy while on therapy use low
molecular weight heparin (LMWH).

- Major surgery =< 4 weeks prior to registration or have not recovered from side
effects of such therapy

- History of other prior malignancies except for properly treated basal cell or
squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer or
early stage prostate cancer

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of confirmed responses defined to be a CR or PR noted as the objective status

Outcome Time Frame:

Every 28 days for up to 2 years

Safety Issue:


Principal Investigator

Patrick Johnston, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

Related Keywords:

  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Peripheral T-cell Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Peripheral
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Lymphoma, Extranodal NK-T-Cell



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