A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)

Key Inclusion Criteria:

• Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition (Rajkumar et al 2014):
• Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder

• Any one or more of the following biomarkers of malignancy:

  1. Clonal bone marrow plasma cell percentage ≥ 60%
  2. Involved: uninvolved serum free light chain ratio ≥ 100
  3. >1 focal lesions on MRI studies
• Patient with measurable disease defined by at least 1 of the following conditions present at screening:
• Serum M-protein by Protein Electrophoresis (PEP) ≥ 1.0 g/dL (≥ 10 g/L).
• Urine M-protein by PEP ≥ 200 mg/24 hours. Involved serum free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal.
• Patient eligible for autologous stem cell transplantation based on the investigator's clinical judgment.
• Patient with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• Patient's age ≥ 18 and \<75 years at time of signing the informed consent
• Patient provided written informed consent prior to any screening procedures
• Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline

Key Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

• Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone; bisphosphonates are permitted only if commenced prior to the start of screening period)
• Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
• Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression
• Patient shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug, following locally applicable prescribing information
• Patient with rade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination at screening
• Patient received prior treatment with DAC inhibitors including Panobinostat
• Patient needing valproic acid for any medical condition during the study or within 5 days prior to first administration of panobinostat/study treatment.
• Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period)

• Patient who received:

  1. prior anti-myeloma chemotherapy or medication including Immunomodulator (IMiDs) and Dex ≤ 3 weeks prior to start of study.
  2. experimental therapy or biologic immunotherapy including monoclonal antibodies ≤ 4 weeks prior to start of study.
  3. prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior start of study.
• Patient has not recovered from all therapy-related toxicities associated with above listed treatments to \< grade 2 CTCAE.
• Patient undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to \< grade 2 CTCAE
• Patients with evidence of mucosal or internal bleeding
• Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 month prior to screening)
• Inability to determine the Fridericia's Correction Formula (QTc) F interval
• Patient with an 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)
• Sexually active males unless they use a condom during intercourse while taking the drug during treatment, and for 6 months after stopping treatment
• Pregnant or nursing (lactating) women.