Multiple myeloma in the relapsed and relapsed/refractory stage MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Panobinostat
Product Code: LBH589-lactate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Panobinostat
CAS Number:
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with a previous diagnosis of multiple myeloma based on IMWG 2003 definitions: o Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation of serum or of total 24 hour urine o Bone marrow (clonal) plasma cells =10% or biopsy proven plasmacytoma o Related organ or tissue impairment (CRAB symptoms, anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections) • Relapsed or relapsed-and-refractory myeloma who have received 1-4 prior lines and now require further treatment • Able to give informed consent and willing to follow study protocol • Aged 18 years or over • ECOG Performance Status = 2 • Required laboratory values within 14 days of registration: o Absolute neutrophil count = 1.0 x 109/L. Growth factor support is not permitted within 14 days prior to eligibility assessment o Platelet count = 100 x 109/L. Platelet support is not permitted within 14 days prior to eligibility assessment o Haemoglobin = 8.0g/dL. Blood transfusion support is permitted o Bilirubin = 2 x upper limit of normal (ULN) o AST and/or ALT = 2.5 x ULN; except in subjects with known hepatic involvement, where AST and/or ALT = 5.0 x ULN o Serum creatinine = 2.0 x ULN o Corrected calcium = 2.8 mmol/L. • Anticipated survival of at least 3 months • Evaluable disease per modified IWG criteria, utilising the following assessments as appropriate: o Serum M protein = 10g/l. o Urine M protein = 200mg/24 hours o Serum free light chain assay: involved FLC level = 100mg/l. Provided serum FLC ratio is abnormal • Female subjects of child-bearing potential must have a negative pregnancy test at baseline and agree to use dual methods of contraception for the duration of the study and must continue to do so for 3 months after the end of treatment. Male subjects must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of child-bearing potential and must continue to do so for 3 months after the end of treatment. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: • Pregnant (positive pregnancy test) or breastfeeding women. • Non-secretory multiple myeloma • Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 28 days before the start of protocol treatment. Steroid therapy is permitted (maximum 160mg dexamethasone or equivalent), but must be stopped 48 hours prior to study drug administration. Bisphosphonates for bone disease and radiotherapy for palliative intent are also permitted. • Concurrent or previous malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer, or incidental histologic findings of prostate cancer (TMN stage T1a or 1b). Patients with histories (=12 months) of other tumours may be entered. • Poorly controlled or serious medical or psychiatric illness that, in the Investigator’s opinion, is likely to interfere with participation and/or compliance in this clinical study • Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy, presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, a history of QTc abnormalities) • Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis. • Gastrointestinal disorders that may interfere with absorption of the study drug • Patients who have been refractory to prior bortezomib, i.e. did not achieve at least an MR, or who have progressed on therapy or within 60 days of last dose • Participants with peripheral neuropathy CTC grade 2 or higher or grade 1 with pain within 14 days prior to registration • Any history of known hypersensitivity to any of the study medication or excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: During the dose escalation phase, the purpose of the study is to determine the maximum tolerated dose (MTD) of panobinostat, administered in combination with VTD, in subjects with relapsed and relapsed/refractory multiple myeloma. In the dose expansion phase the purpose of the study is to estimate the response rate (partial response or better) within 16 cycles of VTD-pano at the RD identified in the dose escalation phase. ; Secondary Objective: Secondary Objectives To confirm the safety profile of panobinostat in combination with VTD To estimate the proportion of participants with each maximum response category within 16 cycles of therapy To estimate time to maximum response to therapy To estimate progression-free survival To assess compliance to therapy To determine the feasibility of panobinostat maintenance Exploratory Objectives To estimate overall survival To estimate the proportion of participants mobilising sufficient stem cells for transplant (out of those undergoing mobilisation) ; Primary end point(s): In the dose escalation phase, the number of participants experiencing DLTs within the first cycle of VTD-pano is the primary outcome. In the dose expansion phase, the primary outcome will be the proportion of participants achieving at least a partial response within 16 cycles of VTD-pano. ; Timepoint(s) of evaluation of this end point: During the dose escalation phase, at the end of each cohort. Final analysis will be carried out when all participants have been followed up for at least 12 months and had response data observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and toxicity Proportion of participants with each maximum response category within 16 cycles of therapy Time to maximum response to therapy Progression-free survival Compliance to therapy Feasibility of panobinostat maintenance Overall survival Proportion of participants mobilising sufficient stem cells for transplant (out of those undergoing mobilisation) ; Timepoint(s) of evaluation of this end point: Final analysis will be carried out on all but the feasibility of panobinostat maintenance endpoint when all participants have been followed up for at least 12 months and had response data observed. The long-term endpoint, feasibility of panobinostat maintenance, will be analysed after the last participant has had their last active trial treatment at which point the progression-free and overall survival endpoints will be updated. | — |
Countries
United Kingdom
Contacts
Public ContactCTRU
University of Leeds CTRU
Outcome results
None listed