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Phase II Trial of Oral LBH 589, a Novel Histone Deacetylase (HDAC) Inhibitor, in Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

Phase 2
18 Years
Not Enrolling
Non-Hodgkin's Lymphoma

Thank you

Trial Information

Phase II Trial of Oral LBH 589, a Novel Histone Deacetylase (HDAC) Inhibitor, in Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

Response Assessment for Mantle Cell Lymphoma

Based on the International Workshop to Standardize Response Criteria to non-hodgkin's
lymphoma (NHL) (Cheson, JCO 1999) a complete hematologic remission will be defined as the

- Disappearance of all evidence of disease.

- Any positron emission tomography (PET)+ mass prior to therapy must be PET negative
after treatment.

- No palpable spleen or liver

- If bone marrow involvement prior to therapy, must document clear bone marrow.

Partial response will be defined as:

- No new areas of disease on clinical exam and regression of previous areas of disease

- Greater than or equal to 50% decrease in the size of prior disease areas per
measurement on computed tomography (CT) scan

- No new PET+ areas on PET scan

- No increase in size of liver or spleen

Response Assessment for CLL

Using the National Cancer Institute (NCI) criteria, a complete hematologic remission will be
defined as having the following present for 2 or more months:

- Absence of symptoms attributable to CLL

- Normal findings on physical examination

- Absolute lymphocyte count <4000/microL

- Absolute neutrophil count (ANC) >1500/microL

- Platelet count >100,000/microL

- Hemoglobin concentration >11 g/dL (untransfused)

- Bone marrow lymphocytosis <30 percent

- No nodules (lymphoid aggregates) on bone marrow biopsy

A partial response per the NCI criteria will be defined as having the following for 2 or
more months:

- A reduction in previously enlarged nodes, spleen, and liver by at · least 50
percent and

- Absolute neutrophil count ≥1500/microL or

- Platelet count ≥100,000/microL or

- Hemoglobin concentration ≥11 g/dL or

- 50 percent improvement over pretherapy reductions in hemoglobin concentration and/or
platelet count

Inclusion Criteria:

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

- Patients must meet the following laboratory criteria (unless dysfunction is due to
organ infiltration by lymphoma):

- ANC ≥ 1.5 x 10^9/L

- Hemoglobin ≥ 9 g/dl

- Platelets ≥ 75 x 10^9/L

- Calculated CrCl ≥50 mL/min (MDRD Formula)

- Total serum calcium ≥ LLN

- Total serum magnesium ≥ LLN

- Aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN

- Serum bilirubin ≤1.5 x ULN

- Serum potassium ≥ LLN

- Thyroid stimulating hormone (TSH) ≥ lower limit of normal (LLN) and free T4
within normal limits. Patients are permitted to receive thyroid hormone
supplements to treat underlying hypothyroidism.

- Baseline multiple uptake gate acquisition scan (MUGA) or echocardiogram (ECHO) must
demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the
institutional normal.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

- Documented MCL by biopsy or CLL by biopsy or flow cytometry.

- Relapsed or refractory disease despite 1 or more lines of therapy.

Exclusion Criteria:

- Prior histone deacetylase (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 ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade

- 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)

- History of ventricular fibrillation or torsade de pointes

- Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ≥
50 bpm.

- Screening 12 lead electrocardiogram (ECG) with a QTc > 450 msec

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

- Myocardial infarction or unstable angina ≤ 6 months prior to starting study drug

- Other clinically significant heart disease (e.g., congestive heart failure (CHF)
New York Heart Association (NYHA) class III or IV , uncontrolled hypertension,
history of labile hypertension, or history of poor compliance with an
antihypertensive regimen)

- Impairment of gastrointestinal (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

- 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.

- Have received either immunotherapy within < 8 weeks; chemotherapy within < 4 weeks;
or radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to
starting study treatment; or who have not yet recovered from side effects of such

- 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). WOCBP must have a negative serum pregnancy
test within 24 hours of receiving the first dose of study medication.

- Male patients whose sexual partners are WOCBP not using effective birth control

- Prior malignancy within the last 5 years (except for basal or squamous cell
carcinoma, or in situ cancer of the cervix)

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

- 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.

- Have not received prior therapy for aggressive MCL or CLL.

- No documentation of disease refractoriness (i.e. progression of disease despite
current therapy or recurrence within 3 months of last treatment) or relapse despite
prior therapy.

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants With Desired Response

Outcome Description:

Investigators intended to assess the rate of overall and complete response by World Health Organization (WHO) classification in patients with relapsed or refractory aggressive mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). WHO Performance Scale Measures levels of patient capability: 0 Normal activity; 1 Symptoms, but nearly fully ambulatory; 2 Some bed time, but needs to be in bed <50% of normal daytime; 3 Needs to be in bed >50% of normal daytime; 4 Unable to get out of bed.

Outcome Time Frame:

8 weeks (2 cycles) unless treatment continues due to partial or complete response

Safety Issue:


Principal Investigator

Celeste Bello, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

March 2011

Related Keywords:

  • Non-Hodgkin's Lymphoma
  • relapsed
  • refractory
  • CLL
  • chronic lymphocytic leukemia
  • MCL
  • mantle cell lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Mantle-Cell



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612