Active clinical trials for "Multiple Myeloma"

Tecemotide (L-BLP25) is believed to induce a Mucinous glycoprotein 1 (MUC1)-specific T-cell response after vaccination. The primary purpose of this study is to ascertain whether vaccination with tecemotide (L-BLP25) induces a MUC1-specific T-cell response in slowly progressive or chemotherapy naive multiple myeloma subjects.

The purpose of this research is to estimate the effectiveness of a response adapted approach with the use of the drug, lenalidomide in the treatment of older adults with newly diagnosed standard risk multiple myeloma. This means that participants will be given the study drug, lenalidomide but depending on how they respond to this drug they may also be given dexamethasone and/or prednisone to help with their treatment.

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Giving bendamustine hydrochloride 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 bendamustine hydrochloride and lenalidomide when given together with dexamethasone and to see how well they work in treating patients with relapsed multiple myeloma.

The patients are being offered a stem cell transplant. Stem cells are very early blood cells. They have not yet matured to become red or white blood cells or platelets. They have already received the standard treatment of chemotherapy and an autologous stem cell transplant. An autologous stem cell transplant is when the patient receives their infusion of their own cells. Thi will give the patient a better chance of curing the disease, this protocol includes an infusion of stem cells from the blood (or the bone marrow) of another person. This is called an allogeneic stem cell transplant. The stem cells will begin to grow in the bone marrow and produce new blood cells. Allogeneic stem cell transplants can cause a condition called graft-versus-host disease or GVHD. In GVHD, a kind of white blood cell from the donor (graft) begins to attack the body (host). That blood cell is called a T-cell. It is a cell that normally helps to protects against things like bacteria and viruses. In this case, the donor's T-cells see the body as foreign in the same way they would see bacteria as foreign. GVHD can be fatal. In order to lower the chance that the patient will get GVHD this protocol treatment will remove the T-cells from the donor's cells. This is called T-cell depletion. The T cells are removed by a system called "Clinimacs". This method is still being evaluated through clinical trials and not been approved by the Federal Drug Administration (FDA) at this time. Before the transplant, the physician will treat the bone marrow to get rid of the cancer. The physician uses three chemotherapy drugs plus ATG. The chemotherapy drugs (Busulfan, Melphalan and Fludarabine) kills the cancer. ATG gets rid of any of the patients T cells that survive the chemotherapy. This ensures that the donor stem cells are not rejected. The patient will also receive additional white blood cells called lymphocytes from the donor. This is called a donor lymphocyte infusion or DLI. These additional infusions will help cause a graft-versus-myeloma effect and can help the donor stem cells grow.

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.

The purpose of the study is to compare thalidomide + dexamethasone with bortezomib + dexamethasone in patients with multiple myeloma refractory to melphalan therapy. The main goal is to find out which of these two 2:nd line regimens that offers the patients the best chance for a response with as long duration and as good quality of life as possible.

To evaluate the safety and maximum tolerated dose (MTD) of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma

The purpose of this Phase I study of vorinostat in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma is to determine the maximum tolerated dose (MTD) as estimated by the incidence of dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D) as estimated by the incidence of drug-related adverse events (AEs).

Intensification with autologous stem cell (ASCT) is currently the most effective treatment for subjects under 65 and the essential goal is to achieve complete response (CR) or very good partial response (VGPR= greater than 90% reduction of monoclonal component). However, only 50% of patients achieve this CR/VGPR even with tandem ASCT early in the course of disease. Optimization of the conditioning regimen could improve this CR/VGPR rate. The combinaison of Velcade and HD Melphalan has never been evaluated. However, at conventional doses, Velcade potentiates the antimyeloma effect of Melphalan without inducing any common toxicity. This study will be conducted in patients under the age of 65 with de novo multiple myeloma or in first relapse, with Salmon and Durie stage of III, II, I with one symptomatic bone lesion (radiological)and no contraindication to intensification. The primary objective will be to increase the CR/VGPR rate 3 months after autologous peripheral blood stem cell transplantation conditioned by Velcade-Melphalan from 40% to 70%. With alpha=5% and bêta=10%, 61 patients will be included. Secondary objectives will be to assess the toxicity of the Velcade-Melphalan conditioning regimen, the progression-free survival and the overall survival after intensification. Response rates will be evaluated according to the response criteria defined by. Analysis will be performed on an intention-to-treat basis. After conventional induction therapy and PBSC collection, patients will be offered this new conditioning regimen. they will be free to refuse this regimen, in which case they will receive standard intensification therapy by Melphalan 200 mg/m² followed by autologous stem cell transplantation. Evaluation will occur at 3 months post intensification.

RATIONALE: Giving chemotherapy before a donor bone marrow transplant or peripheral 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 certain 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 tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide and antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer.