An Open Label Phase II Study on the Use of Panobinostat in Combination with Bortezomib and Dexamethasone as Induction in Multiple Myeloma Patients Candidate to High-Dose Therapy

• Conditions: Multiple Myeloma patients candidate to high-dose therapy; MedDRA version: 14.1Level: PTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-005847-29-IT
• Lead Sponsor: OSPEDALE POLICLINICO S. MATTEO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-02
• Last Update Posted: 13 May 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Diagnosis of Symptomatic Multiple Myeloma based on IMWG 2003 criteria (all three required): • Monoclonal protein present in the serum and/or urine • Monoclonal plasma cells in the bone marrow =10% and/or presence of a biopsy-proven plasmacytoma • Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl or 2 g < normal) [B] Lytic bone lesions or osteoporosis • Patient has to be previously untreated except for emergency use of a short course [maximum 4 days] of steroids. • Patient is between 18 and 65 years of age at time of signing informed consent • Patient has measurable disease, defined as any quantifiable serum M-protein value = 1g/dL and/or urine M-protein of =200 mg/24 hours • Absence of severe associated pulmonary, cardiac, metabolic, neurologic diseases or concomitant neoplasia • Negativity of HBV, HCV, HIV • Performance status score = 60% • Agree to use as acceptable barrier methods for contraception for the duration of the induction phase (for male subject). If female subjects are still having menstrual periods or are not surgically sterile, they must be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and have negative serum beta-HCG pregnancy at screening. • Have pre-treatment clinical laboratory values meeting the criteria specified in the protocol • Patient voluntarily participates by giving written informed consent • Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis • Patient is available for periodic blood sampling, study assessments, and management at the treating institution for the duration of the study • Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of study treatment • Patient should be eligible for an autologous stem cell transplant
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 65
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Diagnosis of smoldering myeloma or MGUS or Waldenstrom’s disease or other conditions in which IgM M-protein is presenting the absence of a clonal plasma cell infiltration with lytic bone lesions. • Diagnosis of plasma cell leukaemia, • Prior or current systemic therapy for multiple myeloma including steroids before randomisation • Prior treatment with HDAC as treatment for cancer except for Valproic Acid used for non-cancer indications such as migraine prevention and seizure disorder. • Radiotherapy within 30 days before entry and with more than 25% of bone marrow reserve irradiated • Plasmapheresis within 30 days before entry • Major surgery within 30 days before entry • Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s) • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances • Uncontrolled diabetes • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 4, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis • Patient has pre-existing NCI CTC Grade 1 neuropathy with pain or =Grade 2 neuropathy • Patient is a regular user or had a recent history (within the last year) of any illicit drugs, or substance abuse • Serious medical or psychiatric illness likely to interfere with participation in the clinical study • Receipt of experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study • Other malignancy within the past 5 years. Exceptions for the following if treated and not active: basal cell or non metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynaecology and Obstetrics stage 1 carcinoma of the cervix • Pregnant or breastfeeding • 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. • Patient is a male not willing to use a barrier method of contraception during the study and for 3 months after the study evaluation completion treatment. • Known hypersensitivity allergy or inability to tolerate any of the agent employed • Patient receiving treatment with any medications which have a relative risk of prolonging the QT interval or inducing Torsades de points.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1. to determine if Panobinostat has an impact on peripheral blood stem cell mobilization (PBSC); 2. to evaluate if this high-dose protocol improves the outcome increasing the overall response rate (ORR), improving time to response (TTR) and prolonging progression free survival (PFS), overall survival (OS), duration of response (DOR), time to progression (TTP), time to next treatment (TNT), treatment free interval (TFI). 3. to determine the feasibility and toxicity of the protocol.;Primary end point(s): Percentage of complete response (CR).;Timepoint(s) of evaluation of this end point: Not applicable.;Main Objective: To evaluate if the combination of Panobinostat, Bortezomib and high-dose Dexamethasone as induction therapy can increase the complete response (CR) rate in subjects with previously untreated multiple myeloma who are candidates to autologous stem cell transplantation (ASCT).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ORR: comprising CR, near CR, VGPR (Very Good Partial Reponse) and partial response (PR); TTR, PFS, OS, DOR, TTP, TNT, TFI. Secondary safety endpoints: AEs, ECG parameters, laboratory parameters;Timepoint(s) of evaluation of this end point: Not applicable.