An Expanded Treatment Protocol of Panobinostat in Combination Therapy for Relapsed, and Relapsed and Refractory Multiple Myeloma

Exclusion Criteria

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• •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
• •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.