Active clinical trials for "Myelodysplastic Syndromes"

RATIONALE: Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of myelodysplastic cells, either by killing the cells or by stopping them from dividing. Tretinoin and decitabine may help myelodysplastic cells become more like normal cells, and to grow and spread more slowly. Giving decitabine together with tretinoin may be an effective treatment for myelodysplastic syndromes. PURPOSE: This phase I/II trial is studying the side effects and best dose of tretinoin when given together with decitabine in treating patients with myelodysplastic syndromes.

Primary Objective: 1. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age > or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents. Secondary Objective: 1. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.

This randomized phase II trial studies azacitidine with or without entinostat to see how well they work compared to azacitidine alone in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may work better in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral 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. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia. PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia

5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS). Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the effects of 5-aza. The goal of this clinical research study is to find the highest safe dose of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness of this combination therapy will also be studied. Additional blood and bone marrow samples will be requested. These samples will be used to evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia and MDS and how the combination of 5-aza, VPA, and ATRA works.

This phase II trial studies the side effects and best dose of total-body irradiation when given together with fludarabine phosphate followed by a donor peripheral stem cell transplant in treating patients with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD). Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target area under the plasma concentration time curve (AUC). Day 0 is the day of hematopoietic progenitor cell reinfusion. Supportive care will be based on institutional guidelines. Blood samples will be collected for dose modification based on the AUC levels. Dose escalation will proceed to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back. In previous research, 5-Azacitidine appeared to help the bone marrow of a patient with MDS begin to function more normally. This means bone marrow cells can grow and do their work the way they were meant to. 5-Azacitidine is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of 5-Azacitidine in patients receiving hematopoietic cell transplants have not been studied.

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

This study is designed to test the combination of decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia