A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Revlimid; Velcade; dexamethasone; Farydak
Intervention description: Revlimid was used with dexamethasone to treat patients with multiple myeloma; Velcade was a proteasome inhibitor indicated for treatment of patients with multiple myeloma; Dexamethasone was a steroid used to treat patients with multiple myeloma.; FARYDAK® (panobinostat) capsules was a prescription medicine used, in combination with bortezomib and dexamethasone, to treat adults with a type of cancer called multiple myeloma after at least 2 other types of treatment have been tried.
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib; Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: multiple myeloma; farydak; panobinostat; LBH589; ASCT; transplant

Summary:

      This was a multicenter, open-label, randomized phase II study which were to enroll 112 newly
      diagnosed symptomatic multiple myeloma patients in a 1:1 fashion. Patients were to enroll at
      approximately 20 centers in the United States.

      Patients were to undergo stem cell mobilization with plerixafor plus Granulocyte Colony
      Stimulating Factor (G-CSF), according to investigator discretion, after 4 cycles of induction
      therapy. Study treatment interruption for stem cell collection were not to exceed 30 days.
      All patients were to receive one additional cycle of study treatment after stem cell
      collection and then proceed to autologous transplant using melphalan 200mg/m2(140mg/m2 for
      patients > 70 years), as conditioning.

      After Autologus Stem Cell Transplant( ASCT), patients still on study were to initiate
      maintenance therapy within the 60-120 day period following ASCT, provided they have adequate
      blood count and clinical recovery. Patients in the RVD arm were to initiate maintenance
      therapy with lenalidomide alone, and patients in RVD-panobinostat arm were to receive
      lenalidomide + panobinostat maintenance. Lenalidomide were to be dosed orally at 10mg/day
      continuously in both arms, increasing to 15mg/day after the first 84 day cycle. Panobinostat
      were to be dosed at 10mg three times a week, every other week. Total planned duration of
      maintenance therapy were to be 3 years.

      Patients were to remain on study treatment until they complete the maintenance phase, or
      until they experience disease progression, unacceptable toxicity, or at the discretion of the
      Investigator.
    

Eligibility criteria:

        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.