A Phase II Study to Investigate Biological Correlates of Clinical Response to Panobinostat in Haematological Malignancy
1. Histologically proven lymphoproliferative neoplasm belonging to one of the following
disease categories that has relapsed or has an incomplete response to conventional
therapy, or where the patient is considered intolerant to conventional chemotherapy
or where no other conventional therapy is considered appropriate.
- Hodgkin lymphoma
- Multiple myeloma (patient must have been exposed to or otherwise unable to
tolerate lenalidomide and bortezomib).
- Peripheral T-cell lymphoma (including angioimmunoblastic lym-phoma and PTCL Not
- Cutaneous T-Cell lymphoma [Mycosis fungoides, Sézary syndrome, Primary cutaneous
gamma-delta T cell lymphoma, Lymphomatoid papulosis, Subcutaneous
panniculitis-like T cell lymphoma Alpha/Beta or lambda/delta type and CD30+
Anaplastic large cell lymphoma]
- Cutaneous B-cell lymphoma [Extranodal marginal zone lymphoma of
mucosa-associated lymphoid tissue (MALT) lymphoma of the skin, Primary cutaneous
follicle cell lymphoma, Primary cutaneous DLBCL, leg type]
- Chronic lymphocytic leukaemia
- Lymphoplasmacytic lymphoma
- B-prolymphocytic leukaemia (or CLL in prolymphocytic transfor-mation)
- T-prolymphocytic leukaemia
2. The lymphoma needs to be accessible, convenient and safe (< 5% risk of bleeding or
serious event) for biopsy in at least one of the following sample types on multiple
occasions as stipulated by the study protocol:
- Peripheral blood samples (absolute peripheral circulating lymphoma cells >
- Bone marrow biopsy (> 30% marrow involvement by lymphoma).
- Clinically apparent cutaneous lymphoma amenable to skin biopsy (patients with
cutaneous involvement and blood stream involvement must agree to biopsies of the
skin in addition to peripheral blood samples).
- Clinically accessible lymph node or extranodal disease amenable to core biopsy.
3. Age ≥ 18 years
4. ECOG performance status score 0-2 at screening.
5. Life expectancy of ≥12 weeks
6. Patient has the following laboratory values within 3 weeks of starting study drug
(labs may be repeated, if needed, to obtain acceptable values before failure at
screening is concluded)
- ANC ≥ 1.5x109 /L
- Platelet count ≥ 100 x 109 /L (unless due to marrow involvement)
- AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
- Serum total bilirubin ≤ 1.5 x ULN (except gilbert's syndrome, in which case ≤ 3
x ULN is required)
- Serum creatinine ≤ 1.5 x ULN
- Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for
serum albumin) or ionized calcium within normal limits
7. Patient has the ability to swallow capsules.
8. Sexually active patient (men and women of child bearing potential) agrees to use
double barrier method of contraception during the course of the study treatment
period (13 cycles) and for 3 months after completing study treatment. WOCBP are
defined as sexually mature women who have not undergone a hysterectomy or who are not
postmenapausal (no menses) for at least 12 consecutive months.
9. Males with a female partner of childbearing potential must agree to use a medically
reliable method of preventing conception throughout the study and for 30 days
following the date of last dose.
10. Mentally competent and is able to understand the information given and provide
informed consent to both the clinical aspects of the study as well as the demands of
the correlative studies and associated tumour biopsies.
1. Concomitant use (within 28 days of first biopsy) of any anti-cancer therapy
including radiation therapy
2. Exposure to a histone deacetylase inhibitor within the preceding 4 weeks.
3. Patient has received chemotherapy or any investigational drug or undergone major
surgery ≤ 2 weeks prior to starting study drug or whose side effects of such therapy
have not resolved to ≤ grade 1 (except for grade 2 neuropathy).
4. Current involvement (medication delivered within 28 days of first biopsy)in a study
of an alternative investigational agent.
5. Impaired cardiac function including any one of the following:
- LVEF < the lower limit of institutional normal, as determined by ECHO or MUGA
- Obligate use of a permanent cardiac pacemaker
- Congenital long QT syndrome
- History or presence of ventricular tachy-arrhythmias
- Resting bradycardia defined as < 50 beats per minute
- QTcF > 450 msec on screening ECG
- Complete left bundle branch block, bifasicular block
- Any clinically significant ST segment and/or T-wave abnormalities
- Presence of unstable atrial fibrillation (ventricular rate > 100 bpm). Patient
with stable atrial fibrillation is allowed in the study provided the other
cardiac exclusion criteria are satisfied.
- Myocardial infarction or unstable angina pectoris ≤ 6 months prior to starting
- Congestive heart failure (New York Heart Association class III-IV)
- Other clinically significant heart disease and vascular disease (e.g.
6. Patient is taking medications with relative risk of prolonging the QT interval or
inducing torsade de pointes, if such treatment cannot be discontinued or switched to
a different medication prior to starting study drug
7. Patient has impairment of GI function or GI disease that may significantly alter the
absorption of panobinostat, such as:
- Active ulcerative disease
- uncontrolled nausea or vomiting
- diarrhea CTCAE grade ≥ 2 (despite antidiarrheal medications)
- malabsorption syndrome
- stomach and/or small bowel resection
8. Known HIV, hepatitis B or hepatitis C (a screening test is not required)
9. Female patients who are pregnant or breast feeding
10. Other concurrent severe and/or uncontrolled medical conditions such as (but not
- uncontrolled diabetes
- active or uncontrolled infection
- chronic obstructive or chronic restrictive pulmonary disease including dyspnea
at rest from any cause
- uncontrolled thyroid dysfunction
- recent, acute or active bleeding
11. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule. This
condition must be discussed with the patient prior to signing consent and
registration in the trial.
12. Prior diagnosis of cancer that was:
- more than 3 years prior to current diagnosis with subsequent evidence of disease
recurrence or estimated clinical expectation of recurrence is greater than 10%
within next 2 years
- within 3 years of current diagnosis with the exception of successfully treated
basal cell or squamous cell skin carcinoma, carcinoma in situ of the cervix or
localised cancer treated curatively with local therapy only.