Active clinical trials for "Leukemia, Lymphoid"

This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. 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 fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.

This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

This phase II trial is studying how well combination chemotherapy with or without donor peripheral stem cell transplant works in treating children with acute lymphoblastic leukemia. Giving combination chemotherapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also helps 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.

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have relapsed or refractory acute lymphoblastic leukemia.

OBJECTIVES: I. Determine the effectiveness of moderate dose cyclophosphamide and radiotherapy in terms of improving survival and reducing the morbidity following allogeneic bone marrow transplantation in patients with myelodysplastic syndrome and acute leukemia related to Fanconi's anemia.

Patients will have immune cells collected and then expanded outside of the body. Patients will receive an infusion of a large number of expanded immune cells. There will be three dose levels studied. The goal of the study will be to determine the safety as well as potential efficacy of this treatment.

Background: Combined therapy with rituximab and fludarabine is the treatment of choice for advanced stage chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). A new technology called deoxyribonucleic acid (DNA) microarray can be used to gain knowledge about the genetic basis of CLL/SLL. Genetic studies of CLL/SLL may improve our understanding of what happens in the disease, help determine which patients are most likely to respond to treatment with fludarabine and rituximab, and identify new treatments. Objectives: -To gain further knowledge about CLL/SLL and the role of rituximab and fludarabine in treating the disease. Eligibility: -Patients 18 years of age and older with low, intermediate or high-risk CLL/SLL. Design: Patients with low-risk CLL/SLL do not receive treatment, but are followed every 3 to 6 months and donate cells (through apheresis) or lymph nodes, or both, for research purposes. Patients with intermediate or high-risk CLL/SLL receive standard treatment with rituximab and fludarabine for six 28-day treatment cycles. Rituximab is given on day 1 and fludarabine is given on days 1-5. (For the first cycle only, fludarabine treatment starts on day 2. This delay permits blood sampling on day 1 for the effect of rituximab on white blood cells.) Laboratory tests and imaging studies are done periodically to monitor drug side effects and the response to treatment. Tests include bone marrow biopsy and aspiration, blood tests and x-rays, including positron emission tomography (PET) and computed tomography (CT) scans.

Allogeneic peripheral blood stem cell transplantation (PBSCT) is primarily limited by graft-versus-host disease (GVHD). In murine models, we have demonstrated that donor CD4+ T cells of Th1 cytokine phenotype (defined by their secretion of IL-2 and IFN-gamma) mediate GVHD. In contrast, donor CD4+ T cells of Th2 phenotype (defined by their secretion of IL-4, IL-5, and IL-10) do not generate GVHD, and abrogate Th-1-mediated GVHD. Importantly, we have demonstrated that enrichment of murine allografts with Th2 cells reduces GVHD without impairing the ability of donor T cells to prevent graft rejection. These studies indicate that the administration of Th2 cells after allogeneic transplantation represents a strategy for achieving alloengraftment with reduced GVHD. In addition to GVHD, allogeneic PBSCT has been limited by the toxicity associated with conventional myeloablative preparative regimens. Such regimens, which typically utilize total body irradiation (TBI) and high-dose chemotherapy, were once considered essential for the prevention of graft rejection. However, recent clinical studies have shown that non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. In murine models, we have demonstrated that severe host T cell depletion induced by combination fludarabine and cytoxan can prevent even fully-MHC mismatched marrow graft rejection. Although non-myeloablative regimens may reduce regimen-related toxicity, such transplants have been associated with a 30 to 40% incidence of severe acute GVHD that is similar to rates observed with myeloablative regimens. Because non-myeloablative regimens appear to be associated with reduced regimen-related toxicity, we have elected to conduct this phase I study of Th2 cells in the setting of an immunoablative (non-myeloablative) preparative regimen. Patients with leukemia in clinical remission, and patients with refractory lymphoid malignancy will be candidates for this HLA-matched allogeneic PBSCT protocol. Patients will receive novel induction regimen (fludarabine and EPOCH) and transplant preparative regimen (fludarabine and cytoxan) designed to maximally deplete host immune T cells capable of mediating graft rejection. After induction and preparative regimen chemotherapy, patients will receive an unmanipulated, G-CSF mobilized PBSC graft. In the initial six patients receiving this transplant procedure at the NCI, graft rejection has been successfully prevented (100% donor chimerism by day 30 post-transplant). Importantly, GVHD has been observed in all six patients, with three of the six patients developing severe GVHD (grade III). Given that this regimen successfully achieves donor engraftment, and is associated with significant GVHD, this transplant regimen represents an excellent clinical setting for the evaluation of Th2 cells. Using this non-myeloablative allogeneic PBSCT approach, we will perform a Phase I study to evaluate the safety and feasibility of administering donor Th2 cells on day 1 post-transplant. Prior to transplantation, donor CD4+ T cells will be stimulated in vitro using culture conditions that support the generation of donor CD4 cells of the Th2 cytokine profile. If this Phase I study demonstrates that Th2 cell administration is safe and feasible, a Phase III study will be performed to evaluate whether Th2 cell administration reduces the incidence and severity of GVHD. Successful implementation of this Th2 strategy will greatly reduce the morbidity and mortality associated with allogeneic PBSCT, and may also represent an approach to stem cell transplantation in patients lacking an HLA-matched donor.

Cancers of the blood, sometimes referred to as hematologic malignancies, are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow. These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms. The disease is life threatening because it blocks the normal function of the marrow, which is to produce red cells (preventing anemia), white cells (preventing infection), and platelets (preventing progression). Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies. However, BMT is a complicated procedure and can be associated with dangerous side effects. In this study researchers are attempting to find ways to reduce the complications of BMT, so that it would be possible to use it more safely and can be offered more patients. In order to do this, researchers are developing new techniques to make BMT safer. It requires making small changes to the standard procedure, which may improve the outcome. The experimental procedures researchers are evaluating are: <TAB>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation <TAB> Cyclosporine given immediately after the transplant <TAB>Add-back of donor lymphocytes Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur. Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies.

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and combining drugs in different ways may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating children who have very high risk acute lymphocytic leukemia.