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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01658241




Registration number
NCT01658241
Ethics application status
Date submitted
20/07/2012
Date registered
6/08/2012
Date last updated
6/05/2022

Titles & IDs
Public title
Panobinostat Biological Correlates Study
Scientific title
A Phase II Study to Investigate Biological Correlates of Clinical Response to Panobinostat in Haematological Malignancy
Secondary ID [1] 0 0
12/18
Universal Trial Number (UTN)
Trial acronym
VEG VCA1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nodal Lymphoma 0 0
Lymphoma With Cutaneous Involvement 0 0
Lymphoma in Leukemic Phase 0 0
Marrow Involvement With Lymphoma 0 0
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - panobinostat

Experimental: Single Arm Main population -


Treatment: Drugs: panobinostat
40mg, three times a week, oral pill over 12 cycles, 4 weeks per cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in gene expression profile of tumor samples taken before and after treatement with panobinostat
Timepoint [1] 0 0
Up to two years from trial entry
Secondary outcome [1] 0 0
Overall response (OR): this is a composite clinical endpoint including those who have achieved a complete remission (CR) or partial remission (PR) by conventional disease-appropriate criteria. (i.e. OR=CR+PR)
Timepoint [1] 0 0
Up to two years from trial entry
Secondary outcome [2] 0 0
Clinical benefit: a composite endpoint including those with complete remission, partial remission, marginal response and those with otherwise stable disease that has been maintained for at least 2 cycles of therapy
Timepoint [2] 0 0
Up to two years from trial entry
Secondary outcome [3] 0 0
Time to response: the time from first drug dose to best confirmed response
Timepoint [3] 0 0
Up to two years from trial entry
Secondary outcome [4] 0 0
Time to progression: the time from initial observation of response to confirmed disease progression, or the time from first drug dose to confirmed disease progression
Timepoint [4] 0 0
Up to two years from trial entry
Secondary outcome [5] 0 0
Progression-free survival: time from trial registration to disease progression or death from any cause
Timepoint [5] 0 0
Up to two years from trial entry
Secondary outcome [6] 0 0
Disease-specific biological improvement - as defined in the protocol
Timepoint [6] 0 0
Up to two years from trial entry
Secondary outcome [7] 0 0
Sustained disease-specific biological improvement - as defined in the protocol
Timepoint [7] 0 0
Up to two years from trial entry

Eligibility
Key inclusion criteria
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
otherwise specified)

- 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 >
2x109/L).

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
study drug

- Congestive heart failure (New York Heart Association class III-IV)

- Other clinically significant heart disease and vascular disease (e.g.
uncontrolled hypertension)

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

- obstruction

- 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
limited to)

- 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.

Study design
Purpose of the study
Basic Science
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/07/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/03/2015
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is looking at the effects of Panobinostat, an investigational treatment, on cancer
cells in patients who have Hodgkin lymphoma (a cancer of the immune system with specific
Hodgkin/Reed Sternberg Cells), T-cell lymphoma (a cancer of the immune system with too many T
lymphocytes), chronic lymphocytic leukemia or prolymphocytic leukaemia (immune system with
too many lymphocytes in the blood stream), lymphoplasmacytic lymphoma (immune system with too
many plasma cells or B lymphocytes) or myeloma (a cancer of plasma cells).

Panobinostat is a new drug which has led to disease improvement in some patients with Hodgkin
lymphoma, certain types of T-cell lymphoma, myeloma and some B cell lymphomas. Not all
patients benefit from panobinostat.

The researchers wish to look at the effects of panobinostat on cancer cells. The aim of this
project is find out which patients or diseases are likely to respond to treatment with
panobinostat in the future and to see if there are particular features of the patient or of
the cancer that affects the likelihood of the way individuals respond to panobinostat.

Panobinostat is an oral medication (taken by mouth) that effects the way cancer cells and in
normal cells make proteins. Panobinostat has been used in several clinical trials around the
world. The largest trials generally have fewer than 200 patients and are in Hodgkin lymphoma,
cutaneous T-cell lymphoma, and myeloma where between one in five and one in three patients
have significant improvement in their disease.

Researchers will look at samples of tumour before treatment and during treatment. This will
be one of the first studies to look at how cancer cells change following treatment with this
drug. It is unusual because it requires repeated biopsies of the participant's tumour.
Panobinostat is considered an experimental (or investigational) drug and not approved by any
regulatory authority (such as the Food and Drug Administration, FDA in the USA or by the
Therapeutics Goods and Administration, TGA, in Australia) to treat any type of cancer.
Therefore, Panobinostat is not approved to treat patients who have been diagnosed with
refractory or relapsed cancer.

A total of 30 patients with one of the diseases listed above will be enrolled at Peter
MacCallum Cancer Centre.

It is expected it will take about 2 to 3 years to recruit 30 patients and that on average
patients will take part for six to eighteen months. This time could be shorter or longer
depending on how well the treatment works in each individual. While the trial will take up to
4 years to complete, the science studies may take longer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01658241
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries