View clinical trials related to Neoplasms, Plasma Cell.
Filter by:This study is designed to compare progression-free survival (PFS) from randomization among patients randomized on the BMT CTN 1302 protocol, "Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib after Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma". It is hypothesized that Ixazomib maintenance therapy will result in improved PFS in patients with high-risk multiple myeloma following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) compared to placebo.
Multiple myeloma (MM) is an incurable disease that is characterized by the accumulation of clonal plasma cells in the bone marrow. While MM patients with relapsed disease may achieve responses to subsequent antimyeloma therapies, the duration of response decreases with successive relapses until resistant disease develops. Until recently, the median survival following relapse after induction therapy was approximately one year. The relatively recent US Food and Drug Administration (FDA) approvals of bortezomib (2003) and combination lenalidomide plus dexamethasone (2006) therapies for the treatment of previously treated MM has provided effective therapeutic options that give patients with relapsed or refractory MM the prospect for a prolongation of overall and progression-free survival times. However, MM remains an incurable disease. A clear unmet medical need still exists for additional novel therapeutic options for the treatment of previously treated MM. Plerixafor reversibly inhibits CXCR4 binding to stromal cell derived factor (SDF)-1alpha and was recently discovered to be an effective agent to mobilize CD34+ cells into the peripheral blood. In normal volunteers, administering Plerixafor after 4-5 days of G-CSF resulted in a 3-3.5 fold increase in circulating CD34+ cells. Two phases 3 studies demonstrated that the combination of G-CSF and Plerixafor is superior to G-CSF alone for mobilizing hematopoietic progenitor cells in front-line or as salvage therapy in patients with multiple myeloma. Nevertheless, almost all patients ultimately relapse, and no plateau is observed in the survival curves. At the time of disease recurrence, there is not one standard salvage approach, but instead, various therapeutic options are available, including novel agents-based therapy, administered for a fixed duration of time or until progression. In the pivotal trial for the approval of bortezomib as monotherapy in relapsed and refractory MM, the median PFS was 7 months, whereas in the pivotal trials for the approval of lenalidomide in combination with dexamethasone in the same group of patients, the median time to progression was approximately 11 months. A more recent prospective, randomized, phase 3 study has shown that a triplet combination of bortezomib, thalidomide and dexamethasone (VTD) achieved superior results compared to thalidomide dexamethasone (TD) alone in patients relapsing following ASCT, with a median time to progression of 19.5 versus 13.8 months, respectively. This study suggests that combinations consisting of both an IMiD and a proteasome inhibitor are a valuable option at the time of relapse. However, when a frozen graft is available, it is also possible to repeat high-dose therapy in patients who previously responded to the frontline application of high-dose melphalan and ASCT. Over time, several reports have demonstrated the feasibility of this salvage strategy. The majority of data are available from retrospective studies and are based on single-centre experiences with small numbers of selected patients. In this setting, PFS has been shown to range from 7 to 22 months, and the treatment-related mortality (TRM) was acceptable, ranging from 0 to 8%. Various prognostic factors for prolonged PFS have been described, such as the duration of response to the first high-dose therapy, or the number of lines of therapy prior to salvage ASCT. With this background, this prospective non-interventional multicentre study will aim to collect data on the feasibility of salvage ASCT using a Plerixafor-based stem cell mobilization in relapsed MM, according to Plerixafor label in France. This is a non-interventional study; visit will be performed as usual, according to each center practices. No additional visits will be requested for the study purpose. The date for each visit and any data generated must be recorded on the appropriate eCRF. The study will consist of 3 periods: - An early screening period - Autologous stem cell mobilization period - High dose melphalan therapy and autologous graft infusion and follow-up for12 months after salvage ASCT Inclusion visit This visit may occur up to 28 days before Mozobil® administration. This visit will be performed during the visit of pre-transplant assessment. For the pre-transplant assessment, the procedures are performed routinely before ASCT even if the patient is not included in the study: Stem cell mobilization phase The stem cell mobilization phase is performed according to standard practice of each participating centre. Follow-up visits High dose melphalan administration and autologous graft infusion will be performed according to each centre standard practice. Patients will be followed according to each center practices. The follow-up of this non-interventional study will end 12 months after ASCT. Subjects will be enrolled over a 2 years period. The total duration of the study will be 36 months
The overall aim is to examine whether early initiated, individualized exercise training in patients newly diagnosed with multiple myeloma, irrespective of age and current performance status, will be beneficial for the patients´physical function, level of physical activity and quality of life, pain and bone disease. The investigators will examine the effect of supervised in-hospital exercise training sessions combined with home-based exercise training, initiated at time of diagnosis. The outcomes of interest are physical function, level of physical activity, QOL, pain and bone disease. Furthermore, to describe the disease in patients with newly diagnosed MM in relation to physical function, level of physical activity, QOL, pain and bone condition at time of diagnosis. The investigators hypotheses are: - Individualized exercise starting at time of diagnosis will have positive effects on physical function, physical activity, QOL and pain. - Individualized exercise starting at time of diagnosis will have positive effects on bone disease (bone markers), bone mineral density (BMD) and lean body mass. - A higher level of physical function is associated with a higher level of physical activity, less pain, better QOL, and higher BMD and lean body mass.
This multicenter, open-label, Phase I study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab alone or in combination with daratumumab and/or various immunomodulatory agents in participants with MM who have relapsed or who have undergone autologous stem cell transplantation (ASCT). Cycle length will be 21 days in Cohorts A to C and 28 days in Cohorts D to F.
This is a Phase 1a/1b, multicenter, open-label, two-part study in subjects with relapsed or refractory MM: - Phase 1a: single agent CWP232291. Dose-finding followed by cohort expansion at the maximum tolerated dose (MTD) or optimal dose as determined by the Safety Review Committee (SRC). - Phase 1b: CWP232291 in combination with lenalidomide and dexamethasone. Dose-finding followed by cohort expansion at the combination therapy MTD or optimal dose as determined by the SRC.
The purpose of this study is to compare the effectiveness of bortezomib versus thalidomide in reducing free light chains in the blood of myeloma patients. In addition participants will receive bendamustine (chemotherapy) and dexamethasone (steroids), which increase the effectiveness of both bortezomib and thalidomide. The trial will also study whether an earlier reduction of free light chains increases the chances of the kidneys recovering.
Daratumumab is a new treatment for patients with myeloma. While many patients benefit from this treatment some do not and the mechanism(s) of failure are poorly understood. This study aims to clarify aspects of resistance to treatment with daratumumab in order to improve patient outcomes in the future.
High-dose chemotherapy and autologous stem cell transplantation (ASCT) as part of the up-front treatment of patients with multiple myeloma has been associated with improved disease-free and overall survival in multiple large randomized controlled trials. Following 3-6 cycles of standard induction therapy with biologic agents, consolidation with high dose Melphalan and ASCT has become the standard-of-care approach for fit myeloma patients up to 70 years of age. Single-agent high-dose Melphalan (200mg/m2) is currently the standard-of-care preparative regimen prior to autologous transplant in Myeloma. Historical studies utilizing Busulfan- or Total Body Irradiation-based preparative regimens have yielded similar results to single-agent Melphalan with higher toxicity.
The purpose of the study is to compare the progression-free survival (PFS) of once-weekly carfilzomib dosing in combination with dexamethasone to twice-weekly carfilzomib dosing in combination with dexamethasone in adults with relapsed and refractory multiple myeloma, previously treated with bortezomib and an immunomodulatory agent (IMiD).
Overview of Study Design: This is an open phase II, single-arm, multi-center study to evaluate progression free survival in patients receiving ixazomib in combination with thalidomide and dexamethasone (ITD) followed by an ixazomib maintenance phase of a maximum period of 12 months. The patient population will consist of adult male and female patients with multiple myeloma (MM) with relapsed and/or refractory disease after at least one prior treatment line. In case of enrollment patients will receive ixazomib 4.0mg at days 1, 8, 15, thalidomide 100mg at days 1 to 28 (50mg in patients aged ≥75 years), and dexamethasone 40mg (20mg in patients aged ≥75 years) at days 1, 8, 15 of a 28-day treatment cycle. The proposed number of cycles is 8. Treatment will be discontinued in case of progressive disease or in case of no response after 4 cycles (≤ SD after 4 cycles). After discontinuation of therapy an end of treatment visit (EOT) will be performed within 14 days after the last dose of the last combination treatment cycle. After 8 cycles of ITD therapy, maintenance treatment with 4.0mg ixazomib (3.0mg in patients aged ≥ 75 years at first day of maintenance phase) on days 1, 8, 15 of 28-day cycles will be administered to patients with ≥ MR for a maximum period of 12 months. Patients who completed less than 8 cycles of ITD treatment do not qualify for maintenance phase. Follow-up visits will be performed in 3-monthly intervals until the last patient on ixazomib maintenance therapy has concluded or discontinued the maintenance phase. A safety analysis will be conducted after enrollment of the first 6 patients and completion of at least two cycles in every patient.