Active clinical trials for "Multiple Myeloma"

The purpose of this research study is to determine how multiple myeloma responds when the study drug vorinostat is added to the standard treatment of bortezomib and pegylated liposomal doxorubicin (PLD). After participants complete the three drug combination and if their multiple myeloma has decreased, the investigators also want to learn what effects (both good and bad) when vorinostat and bortezomib are given to people with multiple myeloma over a longer period of time. This type of treatment is called 'Maintenance Therapy'.

The objective of this post market clinical study is to collect prospective clinical data to confirm the efficacy of RF Kyphoplasty for the treatment of pathological fractures of the spine caused by multiple myeloma.

The purpose of this study is to determine the side effects of treatment with the monoclonal antibody anti-PD-L1 (BMS-936559) in subjects with compromised bone marrow function and the dose that should be recommended for use in future studies.

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.

The purpose of this study is to evaluate the safety and effectiveness of using pegylated liposomal doxorubicin and bortezomib in the treatment of patients with relapsed multiple myeloma who had been previously treated with bortezomib. Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. These cells are part of the immune system, which helps protect the body from germs and other harmful substances. In time, myeloma cells collect in the bone marrow and in the solid parts of bone. Multiple myeloma treatment may include stem cell transplantation, however, not all patients with multiple myeloma are candidates for stem cell transplantation and many patients who receive transplants relapse. As a result, additional first and later-line therapeutic options are needed for patients who are not candidates for transplantation, or whose disease relapses after transplantation or other therapies. Pegylated liposomal doxorubicin in combination with bortezomib is approved for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy. The combined use of pegylated liposomal doxorubicin and bortezomib in this study is designed to evaluate the overall response rate and safety in patients with multiple myeloma who have been previously treated with bortezomib.

Chemotherapy-induced oral mucositis is the inflammation of the oral mucous membranes, which are tissues that line the mouth. Oral mucositis is caused when chemotherapy attacks and kills the rapidly-dividing cells in the oral mucous membranes. This condition feels like sunburn (or heartburn) on the mucous tissues, and often leads to sores in the mouth or on the tongue. This can cause discomfort, pain, difficulties in eating, and a longer hospital stay. Several therapies appear to either prevent or reduce the severity of mouth ulcers caused by chemotherapy for multiple myeloma. Different strategies are used to try and prevent this condition; a small number of trials found that some of these strategies may be effective. None of the trials had compared head to head the use of saline solution (our standard of care), cryotherapy (ice chips) and Caphosol in patients receiving high-dose melphalan. The goal of this research study to evaluate the effectiveness of saline solution, cryotherapy, Caphosol for the prevention of oral mucositis in patients with multiple myeloma receiving high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. The researchers hope to learn if there are any differences among saline solution, cryotherapy and Caphosol mouth rinse for the prevention of oral mucositis.

RATIONALE: Cyclosporine eye drops may prevent graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder. PURPOSE: This randomized phase I trial is studying how well cyclosporine eye drops work in preventing graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder.

Multiple myeloma is a malignant hematological disease dominated by monoclonal plasma cells in the bone marrow. Major symptoms are related to the bones due to an increased bone resorption and a decreased bone formation leading to bone pain and increased risk of fractures. The normal osteoclasts are responsible for bone degradation through stimulation from the malignant plasma cells. Bisphosphonates have been shown to inhibit the osteoclast activity but may have serious side-effects due to renal toxicity and the optimal dose have not been established. In a randomized double blinded design it is aim to compare the standard of monthly injections of 90 mg pamidronate with 30 mg. The primary end-point is physical function estimated by EORTC QLQ-C30 questionnaire at 12 months after starting the treatment in newly diagnosed treatment demanding multiple myeloma. Secondary end-points are skeletal related events, cost-utility analysis, response, response duration and survival and quality of life with respect to fatigue and pain.

This study investigates whether the prophylactic use of moxifloxacin during high-dose chemotherapy followed by autologous stem cell transplantation reduces the incidence of clinically significant bacteremia. Further investigations include time to occurrence of fever, duration of fever, overall survival and antibiotic sensitivity of blood isolates.

Intensive chemotherapy is associated with significant thrombocytopenia, often requiring platelet transfusion to maintain platelet counts. This investigational drug has demonstrated the ability to increase platelet counts. This study will test the safety and efficacy of this investigational drug in the prevention of thrombocytopenia in patients with solid tumors, lymphomas or multiple myeloma who are receiving myelosuppressive treatment regimens requiring platelet transfusion support.