Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
This trial is active, not recruiting.
|Treatment||carfilzomib and panobinostat|
|Phase||phase 1/phase 2|
|Sponsor||SCRI Development Innovations, LLC|
|Collaborator||Onyx Therapeutics, Inc.|
|Start date||December 2011|
|End date||October 2016|
|Trial size||80 participants|
|Trial identifier||NCT01496118, SCRI MM 27|
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 inhibitor which has shown synergistic cytotoxicity in vitro and in vivo with proteasome inhibitors. The combination should enhance the activity of both agents against myeloma cells. In Phase I, the optimal doses of the combination of carfilzomib and panobinostat will be determined. Assuming this combination is feasible, the Phase II portion will proceed using the doses determined in Phase I.
|United States||No locations recruiting|
|Other Countries||No locations recruiting|
|Denver, CO||Colorado Blood Cancer Institute||no longer recruiting|
|Fort Myers, FL||Florida Cancer Specialists South||no longer recruiting|
|Pensacola, FL||Woodlands Medical Specialists||no longer recruiting|
|St. Petersburg, FL||Florida Cancer Specialists North||no longer recruiting|
|Terre Haute, IN||Providence Medical Group||no longer recruiting|
|Terre Haute, IN||RHHP/Hope Cancer Center||no longer recruiting|
|Kansas City, MO||Research Medical Center||no longer recruiting|
|Morristown, NJ||Hematology-Oncology Associates - Northern NJ||no longer recruiting|
|Cincinnati, OH||Oncology Hematology Care, Inc.||no longer recruiting|
|Lawton, OK||Cancer Centers of Southwest Oklahoma||no longer recruiting|
|Chattanooga, TN||Tennessee Oncology-Chattanooga||no longer recruiting|
|Nashville, TN||Tennessee Oncology||no longer recruiting|
|Fort Worth, TX||The Center for Cancer and Blood Disorders||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Phase 1: Number of patients with adverse events as a measure of safety and tolerability
time frame: 6 months
Phase II: overall response rate
time frame: 18 months
time frame: At baseline and every 2 cycles (8 weeks), projected 24 months
time frame: At baseline and every 2 cycles (8 weeks), projected 24 months
time frame: Every 8 weeks until progression then every 3 months thereafter, projected 24 months.
Male or female participants at least 18 years old.
Inclusion Criteria: 1. Eligible participants must have multiple myeloma using standard criteria. 2. 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 3. 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. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. 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.) 6. Ability to swallow oral medications. 7. Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional limits of normal. 8. Male or females ≥ 18 years of age. 9. Female patients must not be of child-bearing potential or must agree to use adequate contraceptive measures. 10. Male patients willing to use adequate contraceptive measures. 11. Willingness and ability to comply with the trial and follow-up procedures. 12. Ability to understand the nature of this trial and give written informed consent. Exclusion Criteria: 1. 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. 2. Previous treatment with HDAC, DAC, HSP90 or valproic acid for treatment of cancer. 3. Requires valproic acid for any medical condition during the study ≤5 days prior to first panobinostat treatment. 4. Patient has not recovered from all therapy-related toxicities associated with prior treatments to < Grade 2 CTCAE. 5. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib). 6. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis ≤14 days prior to study entry. 7. 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. 8. Patients with > grade 2 diarrhea. 9. Patients with impaired cardiac function. 10. Infection requiring IV antibiotics. 11. Patients with > grade 2 peripheral neuropathy or with uncontrolled pain. 12. Women who are pregnant or lactating. 13. Any concurrent medical illness that may impair the ability of the patient to tolerate study treatment and comply with the requirements of the study. 14. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study. 15. 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. 16. 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.
|Official title||Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma|
|Description||This is an open-label, non-randomized Phase I/II study of patients with relapsed or refractory multiple myeloma. A maximum of four dose levels were evaluated during the Phase I portion and no dose-limiting toxicities (DLTs) were observed. In Phase II, patients with relapsed/refractory multiple myeloma will receive treatment with the dose level 4 panobinostat and carfilzomib combination. Patients will be reevaluated for response to treatment after each cycle (4 weeks). Patients with objective response or stable disease will continue treatment, with subsequent reevaluations every 4 weeks, until disease progression or unacceptable toxicity occurs. A parallel Phase I study will occur to evaluate a minimum of 3 patients and a maximum of 6 patients following a standard dose escalation design at additional dose levels of the combination of carfilzomib and panobinostat. If these dose levels are found to be tolerable, then additional patients will be recruited into an expansion cohort which will be open at all sites; a maximum of 36 patients (including those recruited into the parallel Phase I study) will be treated at this dose level. Sites will be notified about the expansion cohort and patients will enter in the dose level confirmed in their enrollment confirmation from SCRI Innovations. Up to 80 eligible patients will be treated in the Phase I/II study.|
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