A multicenter, randomized, double-blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma
- Conditions
- Multiple Myeloma (MM), relapsed or relapsed-and-refractoryMedDRA version: 17.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
- Registration Number
- EUCTR2009-015507-52-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 768
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 should have 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 (lab tests may be repeated, as clinically indicated, to obtain acceptable values before screen fail is concluded but supportive therapies are not to be administered within the week prior to screening tests for absolute neutrophil count or platelet counts)
a.Absolute neutrophil count (ANC) = 1.5 x 109 /L
b.Platelet count = 100 x 109 /L
c.Serum potassium, magnesium, phosphorus, within normal limits (WNL) for institution
d.Total calcium (corrected for serum albumin) or ionized calcium = LLN, 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:
e.AST/SGOT and ALT/SGPT = 2.5 x ULN
f.Serum total bilirubin = 1.5 ULN (or = 3.0 x ULN if patient has Gilbert syndrome)
g.Serum creatinine levels = 1.5 x ULN, or calculated creatinine clearance = 60 ml/min
8.Patient h
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, including any one of the following:
a.LVEF < LLN of institutional norm, as determined by ECHO or MUGA
b.obligate use of a permanent cardiac pacemaker
c.congenital long QT syndrome
d.history or presence of ventricular tachy-arrhythmias
e.resting bradycardia defined as < 50 beats per minute
f.QTcF > 450 msec on screening ECG
g.complete left bundle branch block (LBBB), bifascicular block
h.any clinically significant ST segment and/or T-wave abnormalities
i.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.
j.myocardial infarction or unstable angina pectoris = 6 months prior to starting study drug
k.symptomatic congestive heart failure (New York Heart Association class III-IV)
l.other clinically significant heart disease and vascular disease (e.g. uncontrolled hypertension)
16.Patient taking medications with relativ
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method