Active clinical trials for "Myelodysplastic Syndromes"

The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.

RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect. PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .

Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).

Allogeneic hematopoietic transplant is curative for many patients with hematological neoplasms but conditions to provide optimal engraftment and anti-tumor efficacy with minimal toxicity are still under way. Clofarabine is a newly licensed agent with dramatic anti-leukemic activity. Its incorporation into a regimen for pre-transplant conditioning of acute leukemia and lymphoma patients is logical, exploiting both the anti-tumor activities it is recognized to have and the immunosuppressive activity seen with drugs in its class.

This will be a single arm Phase II study.

This study is designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia.

This study is for patients with relapsed of disease after allogeneic bone marrow The donor's T cells are activated by exposure to 2 compounds or antibodies that bind (or stick to) two compounds on T cells called CD3 and CD28. When these antibodies stick to both CD3 and CD28 on the T cells, the T cells becomes stimulated (or "activated") and grows. CD3 and CD28 are the coating of a T cell and a T cell is part of the body's immune system. It is believed that when T cells are exposed to both of antibodies to CD3 and CD28 compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections or cancer cells. We call this therapy "activated donor lymphocyte infusions, or activated DLI (aDLI)". This current study is being performed to see whether it is safe and effective to administer higher doses of activated DLI or repeated doses of activated DLI. All patients will receive standard donor lymphocyte infusions first, and in addition will receive activated donor lymphocytes approximately 12 days later (DLI followed by aDLI). Depending on the response to this treatment, and depending on possible side effects (such as graft-vs-host disease as described below), patients in remission will then receive additional aDLI every 3 months for 4 more times, and patients not in remission within 6-12 weeks will receive higher dose aDLI. The timing of the higher dose aDLI will be determined by your physician depending on your disease and the rate of progression of your disease. The aDLI can be given as early as 6 weeks, or as late as 12 weeks (3 months).

The goal of the Phase I part of this clinical research study is to find the highest safe dose of bendamustine that can be given to patients with acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL), Chronic myelogenous (or myeloid) leukemia (CML) in blastic phase, Chronic Myelomonocytic Leukemia (CMML), and myelodysplastic syndromes (MDS). The goal of the Phase II part of this clinical research study is to learn if bendamustine can help to control AML, ALL and MDS. The safety of this drug will continue to be studied.

Study and Dose Rationale The safety profile of clofarabine appears acceptable within the target populations studied to date in the clinical studies summarized in Section 2.3. clofarabine has demonstrated anti-cancer activity through inhibition of DNA synthesis and repair, induction of apoptosis, and possibly through other mechanisms. The effect of clofarabine on DNA methylation has not been determined. Numerous responses have been observed after treatment with clofarabine in heavily pre-treated relapsed/refractory patients with ALL or AML. Recently 2 small studies were conducted at the M.D. Anderson Cancer Center looking at the use of clofarabine in the treatment of MDS.31 The first study randomized patients in a Bayesian fashion to 15 vs. 30 mg/m2 given IV daily for 5 days every 4 to 8 weeks. In the 15 mg/m2 arm 3 of 7 patients had a complete remission according to the International Working Group (IWG)32 criteria for response. In the 30 mg/m2 arm, 2 of 6 patients had a complete remission while 1 patient had hematologic improvement according to IWG criteria. In the second study, patients were treated with oral clofarabine at a dose of 40 mg/m2 daily for 5 days every 4 to 8 weeks. Two of 7 patients had hematologic improvement according to IWG criteria. The main toxicities in both trials were prolonged myelosuppression and liver function abnormalities. Preclinical animal models have shown increased clofarabine activity against multiple different tumors with repetitive daily dosing for prolonged periods of time.33 The use of an oral therapy is advantageous for the treatment of a chronic malignancy such as MDS. Furthermore, based on the pre-clinical data mentioned above daily repetitive dosing over a protracted period may provide increased efficacy. Since most MDS patients are elderly and may not tolerate aggressive therapy, a schedule of administration of low dose oral clofarabine over a protracted period may provide the advantage of increased efficacy without severe toxicity. The safety of a protracted daily dosage of oral clofarabine in humans has not been determined. The dosing scheme for this study will therefore include a dose escalating phase I component followed by a phase II component. The starting dose will be 5 mg (fixed dose) orally daily for 10 days. This dose will be escalated in cohorts of 3 patients as tolerated up to a maximal dose of 15 mg (fixed dose) orally for 10 consecutive days. Note that at the latter dose a patient will receive a total of 150 mg of clofarabine per cycle, which far lower than the MD Anderson study of oral clofarabine in MDS whereby patients received 200 mg/m2 per cycle. OBJECTIVES: Study Overview The purpose of this study is to determine the efficacy and toxicity of Clofarabine administered orally at a low daily dose for the treatment of myelodysplastic syndromes.

This study will be used to determine the maximum tolerated dose of oral clofarabine when administered daily for 14 consecutive days repeated every 21 days.