View clinical trials related to Neoplasms, Plasma Cell.
Filter by:The purpose of this study is to evaluate the safety and efficacy of NOX A12 alone and in combination with a background therapy of bortezomib and dexamethasone (VD) chemotherapy in previously treated patients with multiple myeloma (MM).
This randomized pilot phase II trial studies how well giving dalteparin, lenalidomide, and low-dose dexamethasone together works in treating patients with previously untreated multiple myeloma. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with lenalidomide and dexamethasone for multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dalteparin, lenalidomide, and dexamethasone together may be an effective treatment for multiple myeloma
The aim of this trial is to determine whether bortezomib improves response and delays progression for multiple myeloma patients after high dose therapy and autologous stem cell transplant. It will also assess the effect of bortezomib treatment on patient bone health.
Patients with Multiple Myeloma (MM) are at increased risk of venous thromboembolic event, especially in newly diagnosed patients and during induction treatment with thalidomide in combination with dexamethasone. This association was mainly heightened during the 3 first months of chemotherapy. Several coagulation abnormalities have been described. Laboratory tests measuring the overall thrombophilic tendency might be useful to assess thrombosis risk. The aim of this study is to compare thrombin generation by calibrated automated thrombogram during the 3 first cycles of chemotherapy in patients with newly diagnosed MM.
This phase I trial studies the side effects and best dose of yttrium Y 90 anti-CD45 monoclonal antibody BC8 when given together with fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant in treating patients with multiple myeloma. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving yttrium Y 90 anti-CD45 monoclonal antibody BC8, fludarabine phosphate, and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening and may be an effective treatment for multiple myeloma.
Phase IIb clinical trial to determine if resistance to a lenalidomide containing regimen can be overcome by the addition of vorinostat, in patients with relapsed and refractory multiple myeloma.
Histone deacetylase (HDAC) inhibitors represent a potential new class of antitumor agents. Vorinostat (suberoylanilide Hydroxamic acid, SAHA) inhibits the activity of all 11 known human class I and II HDACs. HDACs have many protein targets whose structure and function are altered by acetylation, including histones and non-histones proteins component of transcription factors controlling gene expression and proteins that regulate cell proliferation, migration and death (1). Vorinostat has undergone initial evaluation in several phase I and II clinical trials in both solid and hematologic malignancies. It has shown activity in hematologic malignancies including Hodgkin's disease and non Hodgkin's lymphomas (2-5); it has been approved for treatment of cutaneous manifestation in patients with primary cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies (6). HDAC function is critical for Multiple Myeloma (MM) cells by actively maintaining a transcriptional program indispensable for their uncontrolled proliferation and/or inappropriate resistance to pro-apoptotic stimuli. The pleiotropic anti-MM effects of Vorinostat and its ability to sensitize MM cellsto multiple conventional or novel agents (7) provide the framework for clinical trials of Vorinostat in MM. A phase I trial of oral Vorinostat alone in advanced MM shows modest activity, but treatment was generally well tolerated (common drug related adverse events (AEs) included fatigue, anorexia, dehydration, diarrhea and nausea and were mostly grade < 2) (8). A phase I clinical trial of Vorinostat in association with Bortezomib in relapsed MM patients report a partial response (PR) rate of 42%, with responses occurring also in patients refractory to a previous Bortezomib based regimen. Treatment was generally well tolerated (main adverse events were myelosuppression, fatigue and diarrhea) (9). Lenalidomide is an active agent against MM, that as shown activity in both the relapse and newly diagnosed settings, in combination with chemotherapy or steroids only. The dose of Lenalidomide commonly used in the relapse setting, in association with steroids, is 25 mg/day on days 1-21 every 28 days (10, 11). A recent phase I study evaluated the safety and tolerability of Vorinostat in combination with Lenalidomide and Dexamethasone in relapsed patients:no dose limiting toxicities prohibited dose escalation, the maximum tolerated dose has not been reached and the maximum administered dose was Lenalidomide 25 mg/day on days 1-21, Dexamethasone 40 mg/day on days 1,8,15,22, Vorinostat 400 mg/day on days 1-7 and 15-21; each cycle was repeated every 28 days. Rate of at least PR was 51%, and activity was seen also in patients who received prior Lenalidomide therapy (clinical benefit reported in 69% of patients, including minimal response or better in 33% of Lenalidomide refractory patients). The most common drug related grade > 3 AEs were neutropenia, thrombocytopenia, diarrhea, anemia and fatigue (12). Since Vorinostat has shown efficacy also in patients previously treated with Lenalidomide, and in patients refractory to Lenalidomide, the investigators hypothesis is that the addition of Vorinostat and low-dose dexamethasone to Lenalidomide (ZLd), in patients experiencing a biochemical relapse during a Lenalidomide maintenance ongoing therapy, can overcome Lenalidomide-drug resistance and result in a significant response rate, that can translate into a significant improvement in survival of MM patients. The second hypothesis is that, since the dose of Lenalidomide commonly administered in maintenance therapy, is 10 mg days 1-21 every 28 days, the increase in Lenalidomide dose to the standard dose used for relapsing patients, plus low-dose Dexamethasone (Ld), in patients experiencing a biochemical relapse during a Lenalidomide ongoing maintenance, can as well overcome Lenalidomide-drug resistance and determine a significant response rate, that can translate into a significant improvement in survival of MM patients. This is a multicenter non comparative, randomized, open label, phase II study. Patients, who are receiving Lenalidomide maintenance treatment with or without prednisone, will be randomized to receive: Cohort 1: ZLd association: Lenalidomide orally at the dose of 25 mg/day for 21 days every 28 days Vorinostat orally at the dose of 400 mg/day on days 1-7 and 15- 21 on a 28-day cycle. Dexamethasone orally at the dose of 40 mg day 1,8, 15, 22 every 28 days. Cohort 2: Ld association: Lenalidomide orally at the dose of 25 mg/day for 21 days every 28 days Dexamethasone orally at the dose of 40 mg day 1,8, 15, 22 every 28 days. Patients must have a -confirmed diagnosis of relapsed multiple myeloma. In this Phase II study, a total of up to 35 patients in the ZLd cohort and 48 in the Ld cohort will be enrolled. It is anticipated that full accrual to this study will take approximately 36 months.
New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.
The purpose of this study is to determine the maximum tolerated dose (MTD) of pomalidomide in combination with bortezomib and low-dose dexamethasone in subjects with relapsed or refractory multiple myeloma
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.