Eligibility Details:
Inclusion Criteria:
- Written informed consent must be obtained prior to any screening procedures
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. 1. Patient's age is ≥ 18 years at the time of signing informed consent
2. 2. Patient has a previous diagnosis of multiple myeloma, based on IMWG 2014
definitions. All three of the following criteria had been met:
- Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation
on serum or on total 24 hour urine (or demonstration of M protein in cytoplasm of
plasma cell for non-secretory myeloma).
- Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma
- Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic
bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent
infections)
3. 3. Patient with multiple myeloma (Palumbo 2014) that is relapsed or relapsed and
refractory to at least twoone prior lines of therapy and requires retreatment.
1. Relapsed, defined by disease that recurred in a patient that responded under at
least two prior therapiesy, by reaching a MR or better, and had not progressed
under current therapy or up to 60 days of last dose of this therapy. Patients
previously treated with bortezomib are eligible.
2. Relapsed-and-refractory to a therapy, provided that patient meets both
conditions:
- patient has relapsed to at least twoone prior lines
- and patient was refractory to at least twoone prior lines by either not
reaching a MR, or progressed while under this therapy, or within 60 days of
its last dose. Patients previously treated with bortezomib are eligible even
if they are deemed refractory (based on results on Panorama 2)
3. Patients who have previously received high dose therapy/autologous stem cell
transplant are eligible.
4. Patients who have undergone allogeneic stem cell transplant and do not have
active graft vs host disease requiring immunosuppressive therapy are eligible.
4. 4. Patient has measurable disease at study screening defined by IMWG 2014 criteria
(Palumbo 2014))
5. 5. A patient treated with local radiotherapy with or without concomitant exposure to
steroids for pain control or management of cord/nerve root compression is eligible.
Four weeks should have lapsed since last date of radiotherapy, which is recommended to
be a limited field. Patients who require concurrent radiotherapy should have entry to
the study deferred until the radiotherapy is completed and 2 weeks have passed since
the last date of therapy.
6. 6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
7. 7. Patient has the following laboratory values within 3 weeks before starting study
drug (lab tests may be repeated, as clinically indicated, to obtain acceptable values
before failure at screening is concluded but supportive therapies [such as
erythropoietin and GCSF] are not to be administered within the week prior to screening
tests for ANC or platelet count)
1. Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
2. Platelet count ≥ 100 x 109 /L
3. Serum potassium, magnesium, phosphorus, within normal limits (WNL) for
institution
4. Total serum calcium (corrected for serum albumin) or ionized serum calcium
greater than or equal to lower normal limits (> LLN) for institution, and not
higher than CTCAE grade 1 in case of elevated value Note: Potassium, calcium,
magnesium, and/or phosphorus supplements may be given to correct values that are
< LLN.
5. AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
6. Serum total bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN if patient has Gilbert
syndrome)
7. Serum creatinine levels ≤ 2.5 x ULN, or calculated creatinine clearance ≥ 30
ml/min
8. 8. Patient is able to swallow capsules
9. 9. Patient must be able to adhere to the study visit schedule and other protocol
requirements
10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at
baseline
Exclusion Criteria:
-
Patients eligible for this study must not meet any of the following criteria:
1. 1. Patient has shown intolerance to bortezomib, dexamethasone or panobinostat or
components of these drugs or has any contraindications to any of these therapies
following locally applicable prescribing information.
2. 2. Patient is refractory to panobinostat
3. 3. Allogeneic stem cell transplant recipient presenting with graft versus host disease
either active or requiring immunosuppression
4. 4. Patient has grade ≥ 2 peripheral neuropathy
5. 5. Patient taking any anti-cancer therapy concomitantly (bisphosphonates are
permitted)
6. 6. Patient has second primary malignancy < 3 years of first dose of study treatment
(except for adequately treated basal or squamous cell carcinoma, or in situ cancer of
the cervix)
7. 7. Patient who received:
1. Anti-myeloma chemotherapy or medication including IMiDs, proteasome inhibitor,
and dexamethasone ≤3weeks prior to the start of study
2. Experimental therapy or biologic immunotherapy including monoclonal antibodies ≤
4 weeks prior to the start of study
3. Prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior
to the start of study
8. 8. Patient has not recovered from all therapy-related toxicities associated with above
listed treatments to < grade 2 CTCAE
9. 9. Patient has undergone major surgery ≤ 2 weeks prior to starting study drug or who
have not recovered from side effects to such therapy to < grade 2 CTCAE
10. 10. Patient with evidence of mucosal or internal bleeding
11. 11. Patient has unresolved diarrhea ≥ CTCAE grade 2
12. 12. Patient has impaired cardiac function, including any one of the following:
1. History or presence of ventricular tachyarrhythmia
2. Resting bradycardia defined as < 50 beats per minute
3. QTcF > 450 msec on screening ECG
4. Complete left bundle branch block (LBBB), bifascicular block
5. Any clinically significant ST segment and/or T-wave abnormalities
6. Presence of unstable atrial fibrillation (ventricular response rate > 100 bpm).
Patients with stable atrial fibrillation can be enrolled provided they do not
meet other cardiac exclusion criteria.
7. Myocardial infarction or unstable angina pectoris ≤ 6 months prior to starting
study drug
8. Symptomatic congestive heart failure (New York Heart Association class III-IV)
9. Other clinically significant heart disease and vascular disease (e.g.
uncontrolled hypertension)
13. 13. Patient taking medications with relative risk or prolonging the QT interval or
inducing Torsades de pointes, if such treatment cannot be discontinued or switched to
a different medication prior to starting study drug
14. 14. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of panobinostat (e.g. ulcerative disease,
uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or
small bowel resection)
15. 15. Patient has any other concurrent severe and/or uncontrolled medical conditions
(e.g., uncontrolled diabetes, active or uncontrolled infection, chronic obstructive or
chronic restrictive pulmonary disease including dyspnea at rest from any cause,
uncontrolled thyroid dysfunction) that could cause unacceptable safety risks or
compromise compliance with the protocol
16. 16. Patient has a known history of HIV seropositivity (a test for screening is not
required)
17. 17. Patient has active or chronic hepatitis B or C with or without evidence of hepatic
insufficiency. However, patients who have received the hepatitis B vaccine or who have
had hepatitis B and cleared the infection may be treated. Patients with hepatitis C
who have undergone treatment with IFN and/or other antiviral agents can be considered
for enrollment on a case by case basis after discussion with Novartis.
18. 18. Patient is a male not willing to use a barrier method of contraception (a condom)
during the study and for 3 months after treatment with study drug has been completed.
19. 19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of
a female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test.
20. 20. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 3 months after the final dose of study treatment. Highly
effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of
the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment.
In case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female subjects on
the study the vasectomized male partner should be the sole partner for that
subject.
- Combination of any two of the following (a+b or a+c, or b+c):
1. Use of oral, injected or implanted hormonal methods of contraception or
other forms of hormonal contraception that have comparable efficacy (failure
rate <1%), for example hormone vaginal ring or transdermal hormone
contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository In case of use of oral contraception women should have been
stable on the same pill for a minimum of 3 months before taking study
treatment.
Women are considered post-menopausal and not of child bearing potential if they have had 12
months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age
appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy
(with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed by
follow up hormone level assessment is she considered not of child bearing potential.
common.study.methods.has-drugs-yes
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