Status:
COMPLETED
Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
Lead Sponsor:
SCRI Development Innovations, LLC
Collaborating Sponsors:
Onyx Therapeutics, Inc.
Novartis
Conditions:
Multiple Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
Relapsed/refractory Multiple Myeloma (MM) is an incurable disorder with a poor prognosis. Carfilzomib is a novel proteasome inhibitor with activity in this setting. Panobinostat is a pan-deacetylase i...
Detailed Description
In this open-label, non-randomized Phase I/II study, a maximum of 4 planned dose levels of carfilzomib and panobinostat were evaluated to determine the maximum tolerated dose (MTD) to administer. The ...
Eligibility Criteria
Inclusion
- Eligible participants must have multiple myeloma using standard criteria.
- Patients must have measurable disease requiring systemic therapy defined as at least one of the following:
- Serum M-protein ≥1 g/dl (≥10 g/l)
- Urine M-protein ≥200 mg/24 hrs
- Serum free light chain assay: involved free light chain level ≥10 mg/dl (≥100 mg/l) provided the serum free light chain ratio is abnormal
- Must have progressed during or after at least one previous bortezomib-containing treatment regimen. Patients who have received previous high-dose therapy/autologous stem cell transplantation are eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Must meet the following laboratory criteria:
- Absolute neutrophil count (ANC) ≥1000/μL;
- Platelets ≥70,000/microL;
- AST or ALT and alkaline phosphatase (ALP) must be ≤ 2.5 x ULN, or ≤ 5 x ULN in patients with plasmacytomas of the liver;
- Total bilirubin ≤ 1.5 x the institutional ULN;
- Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min;
- Serum potassium, calcium, magnesium WNL (These may be corrected prior to starting therapy, to make the patient eligible.)
- Ability to swallow oral medications.
- Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional limits of normal.
- Male or females ≥ 18 years of age.
- Female patients must not be of child-bearing potential or must agree to use adequate contraceptive measures.
- Male patients willing to use adequate contraceptive measures.
- Willingness and ability to comply with the trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Exclusion
- Currently receiving or have received systemic cancer therapy (chemotherapy, biologic therapy) ≤ 21 days of initiating study therapy. For patients receiving small molecule targeted therapy, study treatment may begin \>21 days after last dose or \>5 half lives of previous treatment, whichever is shorter. Patients must have completed radiation therapy ≥7 days prior to starting study treatment. Patients must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities. Dexamethasone or other high-dose steroid therapy must be stopped ≥ days prior to starting study treatment.
- Previous treatment with HDAC, DAC, HSP90 or valproic acid for treatment of cancer.
- Requires valproic acid for any medical condition during the study ≤5 days prior to first panobinostat treatment.
- Patient has not recovered from all therapy-related toxicities associated with prior treatments to \< Grade 2 CTCAE.
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
- Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis ≤14 days prior to study entry.
- Patients using medications that have a risk of prolonging the QT interval or inducing Torsade de Pointes if treatment cannot be discontinued or switched to a different medication prior to receiving study drug.
- Patients with \> grade 2 diarrhea.
- Patients with impaired cardiac function.
- Infection requiring IV antibiotics.
- Patients with \> grade 2 peripheral neuropathy or with uncontrolled pain.
- Women who are pregnant or lactating.
- Any concurrent medical illness that may impair the ability of the patient to tolerate study treatment and comply with the requirements of the study.
- Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
- Use of any non-approved or investigational agent ≤30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
- Presence of other active cancers, or history of treatment for invasive cancer ≤ 5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
Key Trial Info
Start Date :
December 1 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2020
Estimated Enrollment :
80 Patients enrolled
Trial Details
Trial ID
NCT01496118
Start Date
December 1 2011
End Date
December 1 2020
Last Update
February 2 2022
Active Locations (13)
Enter a location and click search to find clinical trials sorted by distance.
1
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
2
Florida Cancer Specialists South
Fort Myers, Florida, United States, 33916
3
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
4
Florida Cancer Specialists North
St. Petersburg, Florida, United States, 33705