None listed
Conditions
Brief summary
The primary purpose of this study is to determine if panobinostat maintenance in patients with multiple myeloma (MM) who have failed to achieve complete remission (CR) following high-dose chemotherapy conditioned autologous stem cell transplantation (ASCT) will lead to an increased/improved rate of conversion to CR or very good partial response (VGPR). You may be eligible to join this study if you have previously been treated with a thalidomide, and/or lenalidomide and/or bortezomib containing induction regimen pre-ASCT. Participants in this trial will receive the oral drug panobinostat at a dose of 45mg three times per week every other week as part of a 4-week (28 day) treatment cycle. You will be treated for 6 cycles and then assessed for response. If after 6 cycles you have not achieved a very good partial response (VGPR) or CR, your panobinostat treatment will cease. If, however, you have achieved the required response, you will continue on panobinostat until disease progression or unacceptable toxicity.
Interventions
Patients will commence treatment with oral panobinostat 45mg three times per week every other week as part of a 4-week (28 day) treatment cycle. Patients will be treated for 6 cycles and then assessed for response. If after 6 cycles patients have not achieved a very good partial response (VGPR) or CR they will cease panobinostat. Patients achieving the required response will continue on panobinostat until disease progression or unacceptable toxicity.
Sponsors
The Alfred Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria at registration - pre-ASCT 1. Age > 18 years 2. Diagnosis of multiple myeloma 3. Must have been previously exposed to thalidomide, and/or lenalidomide and/or bortezomib containing induction regimen pre-ASCT (no more than 12 months total prior standard-dose chemotherapy) 4. No previous high-dose chemotherapy or ASCT 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 6. > 2 X 10^6 CD34+ stem cells available for infusion 7. Normal liver and kidney function (within 2 x the institutional upper limit of normal) 8. Written informed consent Inclusion criteria to commence panobinostat post-ASCT 10. Have reached Day 42 post-ASCT with evidence of haematology recovery (neutrophils > 1.5 x 10^9/L, platelets unsupported > 50 x 10^9/L 11. Have failed to achieve CR and without progressive disease at 6 to 8 weeks post-ASCT 12. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 13. Normal liver and kidney function (within 2 x the institutional upper limit of normal); serum potassium, magnesium, phosphate, sodium, total corrected calcium within normal limits
Exclusion criteria
1. Patients with monoclonal gammopathy of uncertain significance (MGUS) 2. Patient has been treated with allogeneic transplant 3. Patient has received any anti-MM therapy after ASCT including but not limited to: - chemotherapy prior to start of study - biologic immunotherapy including monoclonal antibodies or experimental therapy prior to start of study - radiation therapy 4. Patients with progressive MM post-ASCT 5. Patient has received prior treatment with DAC in ihibitors including panobinostat 6. Patient has received an investigational agent of any kind within 28 days of ASCT 7. Patient is taking any anti-cancer therapy concomitantly 8. Patient needs valproic acid within 5 days prior to first administration of panobinostat 9. Patients with evidence of another malignancy not in remission, or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix) 10. 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 1 CTCAE 4.0 or baseline 11. Patient has impaired cardiac function, including any one of the following: - Left Ventricular Ejection Fraction < the lower limit of institutional norm - Complete left bundle branch block, bifascicular block - Obligate use of a permanent cardiac pacemaker - Congenital long QT syndrome - History or presence of ventricular tachy-arrhythmias - Resting bradycardia defined as < 50 bpm - QTcF > 480 msec on screening ECG - Any clinically significant ST segment and/or T-wave abnormalities - Presence of unstable atrial fibrillation (ventricular response rate > 100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria - Myocardial infarction or unstable angina pectoris < 6 months prior to starting the study drug - Congestive cardiac failure (New York Heart Association class III-IV) - Other clinically significant heart disease and vascular disease (eg. uncontrolled hypertension) 12. Patient is 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 13. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat, such as: - ulcerative disease - uncontrolled nausea - vomiting - diarrhoea CTCAE 4.0 Grade > 2 (despite antidiarrheal medications) - malabsorption syndrome - obstruction - stomach and/or small bowel resection 14. Patient has any other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol such as: - uncontrolled diabetes - active or uncontrolled infection - chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause - uncontrolled thyroid dysfunction - recent, acute or active bleeding 15. Patient has a known history of human immunodeficiency virus (HIV) seropositivity or history of active/treated hepatitis B or C (a test for screening is not required)
Outcome results
None listed