View clinical trials related to Multiple Myeloma.
Filter by:MM accounts for 10% of hematopoietic malignancies. Despite the use of various drug combinations in chemotherapy, life expectancy of MM patients does not exceed 7 years. Until now, lack of specific markers of the disease has not allowed efficient specific molecular targeting. In view of our preliminary results, the antiapoptotic protein Bcl-B could be a novel diagnostic and pronostic marker of MM. Therefore, our main objective will be to confirm that Bcl-B is indeed a novel diagnostic and pronostic marker and a new potential therapeutic target of MM. Targeting Bcl-2 family member's is a promising strategy for the treatment of hematopoietic malignancies. In this context, specific targeting of Bcl-B could improve the treatment of patients suffering MM. Of note, this could be achieved by converting the antiapoptotic function of Bcl-B to a proapoptotic one thanks to the use of small mimetic peptides derived from Nur77 one of its interactors.
Patients with multiple myeloma have seen their survival rate strongly improved with the use of new anti angiogenic agents. Among them, the new chemotherapy with thalidomide or lenalinomide are frequently successfully suggested in therapeutic protocol such as MPT however they can strongly increase the risk of venous thrombo embolic disease (DVT and PTE) up to 20%. In these conditions, a prevention of this risk can be proposed by physician with either low molecular weight heparin (LMWH) anticoagulants or antiplatelets agents. Pending the new recommendations on the management of VTED, the purpose of this study is to describe in real life conditions the management by oncologists of the thrombo embolic risk for such patients
Rationale: We recently reported a study where overall and event free survivals in newly diagnosed myeloma patients receiving an autologous transplant followed by an allograft from an HLA-identical sibling were superior as compared to those undergoing a double autologous transplant. A larger multicenter study by the Gruppo Italiano Trapianti di Midollo (GITMO), co-ordinated by our group and recently closed, employing a tandem auto-allo approach in newly diagnosed patients confirmed the achievement of prolonged event free and overall survival. Importantly, the achievement of at least very good partial remission at the time of allografting conferred a significant advantage in both event-free-survival (HR 0,23, CI 0,11-0,48; p=0,0001) and overall survival (HR 0,26; CI 0,09-0,79; p=0,02). Moreover, recent advances in the understanding of the pathogenesis of multiple myeloma have identified specific signalling pathways that have become targets for biologically-based drugs such as thalidomide, bortezomib and lenalidomide and employed in several trials, including after allograft. The aim of the current proposal is to combine the post-transplant efficacy of graft-vs.-myeloma with the anti-myeloma effect of lenalidomide in newly diagnosed myeloma patients with an HLA-identical sibling treated with a tandem autograft-allograft approach. Maintenance/consolidation of the response may be a key factor to further improve rate of clinical and molecular (as a prelude to cure) remissions and prolong overall and event free survivals after allografting. We would like to investigate the safety and efficacy of lenalidomide as consolidation/maintenance therapy in patient undergoing tandem autologous-allogeneic transplant. Objectives of study: To evaluate 1) toxicity and tolerability of lenalidomide after allografting; 2)To evaluate efficacy of lenalidomide in inducing complete remission, defined as negative immunofixation, 12 months after allografting; 3) overall-survival; 4) event-free survival; 5) molecular remission rate. Furthermore we plan to compare molecular remission rate in patients treated with lenalidomide after tandem auto-allo transplant and after double autologous transplant and to monitor minimal residual disease in patients achieving clinical CR with lenalidomide. Patient Selection: Patients with newly diagnosed multiple myeloma with an HLA identical sibling suitable for PBSC donation will be included. Complete cytogenetic analysis at diagnosis will be required. The patient must have the capacity to give informed consent. Age >18 and < 65. Negative pregnancy test and willing to use contraceptive techniques during and for 12 months following treatment is required. Only very unfitted patients will be excluded. Treatment plan: Lenalidomide will be started at 6 months post-allotransplant at the dose of 10 mg/day continuously in all patients (unless in molecular CR), if the following conditions are present: - absolute neutrophil count > 1 x 109/L without the use of growth factors; - platelet count > 75 x 109/L without transfusion support; - calculated or measured creatinine clearance: ≥ 20 mL/minute; - total bilirubin < 2 x the upper limit of normal, - AST and ALT < 2.5 x upper limit of normal - less than 1 mg/kg/day of prednisone, and no more than 2 immunosuppressive drugs other than steroid to control GVHD (if more immunosuppression is required to control GVHD, the maintenance therapy with lenalidomide will be held until this criteria will be satisfied) Treatment will be continued without interruption, unless not tolerated, until unacceptable adverse events are experienced or progressive disease occurs. Moreover, lenalidomide will be discontinued in patients who achieve and maintain molecular remission for 2 consecutive controls at least 6 weeks apart. Safety section - dose modification plan: During the study patients will be monitored for the occurrence of side effects. Toxicity events will be graded according to the NCI toxicity criteria. In case of severe toxicity, the lenalidomide dose will be reduced or withheld as outlined in the protocols. Statistical section: - Total patient sample size: 53. This is a phase 2 study designed according to a Simon's two-stage Minimax Design. An early stopping rule will be established to interrupt the study in case of futility (a non satisfactory response rate). In stage I 27 patients will be enrolled; if < 14 complete remissions will be observed, the trial will be stopped. In stage II 26 more patients will be enrolled. If ≥ 32 responses will be observed, it will be concluded that the lenalidomide maintenance is active in increasing the complete remission rate after auto-allograft. Analysis plan: Toxicity monitoring will be incorporated into the study design by requiring that the trial be terminated after an initial stage if the number of observed toxicities (treatment related deaths) is excessive.
Complete Response (CR) plus near CR rate of VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy followed by ASCT in patients with newly diagnosed MM was about 50% and CR plus near CR rate of PAD (Bortezomib, Adriamycin, Dexamethasone) induction chemotherapy followed by ASCT in patients with newly diagnosed MM was about 60%. If the CR with near CR rate of sequential high-dose dexamethasone and response adopted PAD or VAD induction chemotherapy followed by ASCT is more than 60%, this combination will be accepted as active regimen that may be worth for investigating in phase III trial. But, if the CR with near CR rate of this regimen is lower than 50%, this has not a merit than VAD induction chemotherapy. Based upon the above assumption, this trial was designed by using Simon's optimal two-stage testing procedure. Assuming a target level of interest, p1=0.6, and a lower activity level, p0=0.5. Initially 61 patients will be accrued. If 33 or more CR + near CR rate were observed, the trial will be continued. Accrual will be planned to a total of 190 patients. If total 106 or more patients were assessed as CR with near CR, sequential high-dose dexamethasone and response adopted PAD or VAD induction chemotherapy regimen will be accepted as active regimen. This design provides probability 0.05 of accepting drugs worse than p0 and probability 0.20 of rejecting drugs better than p1. If we assume that drop-out rate is 10%, total accrual patient will be 210. Patient characteristics and toxicity will be evaluated by descriptive methods. Progression free survival and overall survival (median value, 95% confidence interval) will be calculated by Kaplan-Meier method.
This phase II trial studies how well sirolimus, cyclosporine and mycophenolate mofetil works in preventing graft-vs-host disease (GVHD) in patients with blood cancer undergoing donor peripheral blood stem cell (PBSC) transplant. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also 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 total-body irradiation together with sirolimus, cyclosporine, and mycophenolate mofetil before and after transplant may stop this from happening.
This is a Phase 1 study during which patients with relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL) will receive investigational study drug ARRY-520 and bortezomib, with or without dexamethasone, with granulocyte-colony stimulating factor (G-CSF) support. This study has 2 parts. In the first part, patients will receive increasing doses of study drug (2 dosing schedules will be evaluated) in combination with (1) bortezomib with G-CSF support or (2) bortezomib and dexamethasone with G-CSF support, in order to achieve the highest dose of study drug possible that will not cause unacceptable side effects. Approximately 45 patients from the US will be enrolled in Part 1 (Active, not recruiting). In the second part of this study, patients will receive the best dose(s) and schedule(s) of study drug, in combination with bortezomib ± dexamethasone + G-CSF, determined from the first part of the study and will be followed to see what side effects the combination causes and what effectiveness the combination has, if any, in treating the cancer. Approximately 42 patients from the US will be enrolled in Part 2 (Active, not recruiting).
The aim of this phase I/II trial is to determine the maximal tolerated dose (MTD) of carfilzomib together with pegylated liposomal doxorubicin hydrochloride (PLD) with or without dexamethasone, and then to establish the efficacy and safety of this novel combination in patients with relapsed or refractory multiple myeloma
One purpose of this study is to find out if a new combination of immune system treatments (MAGE-A3 vaccine plus activated T-cells) will allow the body to build up protection ("immunity") against the myeloma cells. A second purpose is to find out how well this combination of immune system treatments is able to control the myeloma.
This is an open label Phase II study to determine the rate of improvement in response of patients with previously treated multiple myeloma to imetelstat alone or in combination with lenalidomide maintenance therapy. This study will include multiple myeloma patients who either have achieved disease stabilization or who have achieved at least a partial response (PR) but failed to achieve a complete response (CR) after cytoreductive therapy for multiple myeloma; ie, have detectable but non-progressing disease and will most likely relapse.
The primary objective of this study is to: • Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan The secondary objectives of this study are to: - Determine the toxicities resulting from administration of combinations of thalidomide, bortezomib and melphalan - Determine the complete response (CR) and very good partial response (VgPR) rate in patients undergoing ASCT using thalidomide, bortezomib and melphalan - Evaluate the treatment-free interval after treatment with the combination of thalidomide, bortezomib and melphalan