Active clinical trials for "Neoplasms, Plasma Cell"

RATIONALE: Drugs used in chemotherapy, such as azacitidine and dexamethasone, work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving azacitidine together with lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with lenalidomide and low-dose dexamethasone in treating patients with relapsed or refractory multiple myeloma.

This study is intended to investigate the combination of the combination of dexamethasone (Decadron®), Clarithromycin (Biaxin®), and pomalidomide (CC-4047®) [ClaPd] in multiple myeloma patients who have relapsed or refractory disease who have failed prior treatment with lenalidomide when used alone or in combination with corticosteroids. Primary endpoint will be response rate to treatment. Secondary endpoints will include toxicity of the combination, time to maximum response, and time to disease progression

Phase I/II trial of Carfilzomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma. Nine: University Hospital of Nantes, University Hospital of Nancy, University Hospital of Lille, University Hospital of Tours, department Hospital of La Roche Sur Yon, University Hospital of Reims, University Hospital of Clermont-Ferrand, University Hospital of Toulouse, University Hospital of Dijon Newly diagnosed symptomatic Multiple Myeloma > 65 years. Treatment comprises an initial phase consisting of nine 6-week cycles of Carfilzomib on Days 1, 2, 8, 9, 22, 23, 29, 30 (carfilzomib is administered at 20 mg/m2 on Days 1 and 2 of the first cycle and 20, 27, 36 or 45 mg/m2 thereafter) followed by a 12 day rest period (42-day cycle), in combination with oral Melphalan 9 mg/m² and oral prednisone 60mg/m², both on days 1 to 4. Phase I: Identification of Maximum Tolerated Dose (MTD) Carfilzomib will be administered at a dose of 20mg/m² for all doses to the first cohort of 6 patients. If dose-limiting toxicities (DLTs) occurred in fewer than 2 of these patients, the next cohort of 6 patients (cohort 2) will receive a dose of 20/27 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 27 mg/m² for all subsequent doses. If DLTs occurred in fewer than 2 of the patients in cohort 2, the third cohort of 6 patients will receive a dose of 20/36 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 36 mg/m² for all subsequent doses. If DLTs occurred in fewer than 3 of the patients in cohort 3 the fourth cohort of 6 patients will receive a dose of 20/45 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 45 mg/m² for all subsequent doses. If at any time during cycle 1 of a dose cohort, ≥ 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrollment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in ≥ 33% (i.e. ≥ 2 of 6) subjects in a cohort. The following are defined as DLTs: Any hematologic toxicity of grade 4 intensity or preventing administration of 2 or more of the 8 carfilzomib doses of the first treatment cycle except a) grade 4 thrombocytopenia without bleeding lasting ≤ 7 days or b) grade 4 neutropenia lasting ≤ 7 days Grade ≥ 3 febrile neutropenia Grade ≥ 3 gastrointestinal toxicities (except for grade ≥ 3 nausea/ vomiting if the patient had not received adequate antiemetic prophylaxis) Any other grade ≥ 3 nonhematologic toxicity considered related to CMP by the principal investigator. Grade ≥ 3 peripheral neuropathy persisting for more than 3 weeks after discontinuation of study drugs. Adverse events (AEs) will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). MTD determination will be based on occurrence of DLTs during the first induction treatment cycle only. Phase II: Expanded Cohort. After identification of the MTD, it is planned for the dose cohort to be expanded to include up to a total of 20 patients treated at the MTD for the phase II part of the study. A full treatment course is the same as for phase I: nine 6-week cycles of CMP. PRIMARY ENDPOINT Phase I: MTD of combination Phase II: Overall response rate [(ORR), consisting of complete response (CR), very good partial response (VGPR), and partial response (PR) SECONDARY ENDPOINTS Safety and tolerability of CMP Clinical benefit response [(CBR = ORR + minimal response (MR)], Progression-free survival (PFS), Duration of response Overall survival (OS). Safety data analysis will be conducted on all subjects receiving at least one dose of study treatment. Analyses will consist of data summaries for reported AEs. The number and percentage of subjects experiencing one or more AEs will be summarized by dose, relationship to study drugs, and severity. AEs will be coded using MedDRA terminology. Disease Response Analyses: Overall response rate (ORR = CR + VGPR + PR) to treatment will be measured using the International Myeloma Working Group (IMWG) criteria. Clinical benefit response (CBR = ORR + MR) will be determined using minimal response (at least 6 weeks duration) as defined by the European Group for Blood and Marrow Transplant (EBMT). The distribution of subjects by response category will be made overall and by dose cohort. Time-to-event endpoints will be evaluated with the use of the Kaplan-Meier method and plots will be provided. Analysis of time-to-event outcomes will be performed for the overall sample.

This pilot phase I trial studies the side effects and the best dose of giving viral therapy to patients with relapsed or refractory multiple myeloma. Viral therapy, such as wild-type reovirus, may be able to kill cancer cells without damaging normal cells.

The goal of this clinical research study is to find the highest tolerable dose of the drug panobinostat that can be given in combination with the drugs Velcade (bortezomib), Revlimid (lenalidomide), and Decadron (dexamethasone) to patients with MM. The safety of this drug combination will also be studied. Panobinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die. Bortezomib is designed to block a protein that causes cells to grow. This may cause cancer cells to die. Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may slow the growth of cancer cells. Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to MM patients in combination with other chemotherapy to treat cancer.

Phase Ib, open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of GSK2110183 dosed in combination with bortezomib and dexamethasone in multiple myeloma (MM) subjects who have failed at least one line of systemic treatment. Part 1 will identify the maximum tolerated dose(s) (MTD) of the combination regimen. Schedule A - GSK2110183 administered once daily with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) given biweekly. Part 2 will further explore the safety, tolerability and clinical activity of the MTD(s) identified in Part 1, including a pharmacokinetic cohort.

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.

The purpose of this study is to determine if bortezomib when added to consolidation treatment with thalidomide and prednisolone leads to an improved response in patients with multiple myeloma who have undergone autologous stem cell transplant and initial treatment with bortezomib, cyclophosphamide, and dexamethasone.

RATIONALE: There are different methods of stem cell mobilization, such as using colony-stimulating factors alone or following chemotherapy priming. More recently, the combination of plerixafor and colony-stimulating factors has been shown to enhance stem cell mobilization. This study will assess whether the combination of plerixafor and Granulocyte Colony-Stimulating Factor (G-CSF) is effective following chemotherapy mobilization with cyclophosphamide. PURPOSE: To assess the safety, tolerability, and best dose of intravenous plerixafor following cyclophosphamide priming.

This study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma.