A multicenter, randomized, double-blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma. - ND

• Conditions: Multiple Myeloma; MedDRA version: 9.1Level: LLTClassification code 10028228

• Registration Number: EUCTR2009-015507-52-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-04
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

1.Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions. All three of the following criteria must have been met: a. Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine b. Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma c. Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections) 2.Patient with 1 to 3 prior lines of therapy who require retreatment of myeloma (cf IMWG 2003 ) for one of the 2 conditions below: a. Relapsed, defined by disease that recurred in a patient that responded under a prior therapy, by reaching a MR or better, and had not progressed under this therapy nor up to 60 days of last dose of this therapy. Patients priorly treated by BTZ may be eligible. b. Relapsed-and-refractory to a therapy, provided that meets both conditions: - patient has relapsed to at least one prior line - and patient was refractory to another line (except BTZ), by either not reaching a MR, or progressed while under this therapy, or within 60 days of its last dose 3.Patient has measurable disease on M protein at study screening defined by at least one of the following measurements as per thresholds clarified in IMWG 2003 disease definitions (Kyle, et al 2003): Serum M-protein ≥ 1 g/dL (≥ 10 g/L) Urine M-protein ≥ 200 mg/24 h 4.Patients treated with local radiotherapy with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy shouldhave entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy 5.Patient s age is ≥ 18 years at time of signing the informed consent 6.Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 7.Patient has the following laboratory values within 3 weeks before starting study drug (SEE TO PROTOCOL) 8.Patient has provided written informed consent prior to any screening procedures 9.Patient is able to swallow capsules 10.Patient must be able to adhere to the study visit schedule and other protocol requirements 11.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at within 7 days prior to start of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients who have progressed under all prior lines of anti MM therapy (primary refractory) 2.Patients who have been refractory to prior BTZ (ie. did not achieve at least a MR, or have progressed under it or within 60 days of last dose) 3.Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression 4.Patient has 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 5.Patient has grade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination within 14 days before randomization 6.Patient received prior treatment with DAC inhibitors including panobinostat 7.Patient needing valproic acid for any medical condition during the study or within 5 days prior to first administration of panobinostat/study treatment 8.Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period) 9.Patient has another primary malignancy < 3 years from first dose of study treatment 10.Patient who received: a. prior anti-myeloma chemotherapy or medication including IMiDs and Dex ≤ 3 weeks prior to start of study. b. experimental therapy or biologic immunotherapy including monoclonal antibodies ≤ 4 weeks prior to start of study. c. prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior start of study. 11.Patient has not recovered from all therapy-related toxicities associated with above listed treatments to < grade 2 CTCAE. 12.Patient has 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 13. Patients with evidence of mucosal or internal bleeding 14.Patient has unresolved diarrhea ≥ CTCAE grade 2 15. Patient has impaired cardiac function:(SEE THE PROTOCOL) 16.Patient 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 17.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) 18. 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 19. Patient has a known history of HIV seropositivity or history of active/treated hepatitis B or C (a test for screening is not required) 20.Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the study evaluation completion treatment, of which one must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e. patient ha

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare progression-free survival (PFS), in patients treated with PAN in combination with BTZ/Dex vs. patients treated with placebo in combination with BTZ/Dex.;Secondary Objective: Key Secondary:To compare OS (overall survival) Other Secondary:-To compare ORR (overall response rate) comprising CR, nCR and PR -To compare MRR (minor response rate)-To compare TTR (time to response)-To compare TTP (time to progression) -To assess duration of response (DOR; from first occurring PR or better)-To assess safety of the combination therapy -To assess health-related quality of life and symptoms of multiple myeloma.;Primary end point(s): Primary efficacy endpoint:PFS (based on modified EBMT criteria, i.e. relapse for patients in CR or in nCR, or PD for patients not in CR nor nCR)