Active clinical trials for "Myelodysplastic Syndromes"

This is a multicentric, non-randomized, non-controlled open-label phase II trial to evaluate the safety and efficacy of treosulfan in a combination regimen with fludarabine as conditioning therapy prior to allogeneic stem cell transplantation (SCT) in patients with haematological malignancies. The aim is to demonstrate a clinical benefit compared with historical data on intravenous busulfan (BusulfexTM, BusilvexTM), the only drug so far registered in the indication conditioning before allogeneic stem cell transplantation.

RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.

This study is mainly assessing the safety of Revlimid in combination with Ancestim (recombinant human stem cell factor) in patients with symptomatic myelodysplasia. Of those two compounds, Revlimid has been shown to be an active drug in myelodysplasia. Clinical responses will also be assessed.

Phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD123-CD33 cCAR in patients with relapsed and/or refractory, high risk hematologic malignancies.

Phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CLL1-CD33 cCAR in patients with relapsed and/or refractory, high risk hematologic malignancies.

The study will be an open label, single arm, phase I study intended to identify the safety and tolerability of "AML Cell Vaccine" given to eligible MDS RAEB-2 and AML patients who have achieved a best response of complete remission or partial remission following their first or second course of standard induction chemotherapy.

Phase 1 will investigate maximum tolerated dose of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS. Phase 2 will investigate overall response rate of OXi4503 in combination with intermediate-dose cytarabine in 1) subjects with MDS after failure of 1 prior hypomethylating agent (Arm A) and 2) subjects with relapsed and refractory AML after treatment failure of up to 1 prior chemotherapy regimen (Arm B).

RATIONALE: Giving chemotherapy and total marrow and lymphoid irradiation before allogeneic hematopoietic cell transplant helps stop the growth of leukemia 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 achieve brand new hematopoietic recovery. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, resulting in graft versus-host disease. PURPOSE: This study is to evaluate the toxicity and efficacy of total marrow and lymphoid irradiation conditioning when given together with combination chemotherapy and allogeneic peripheral blood stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia.

Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not cured with conventional therapy and new approaches are needed. For the last 15 years we have investigated the potential of using a patient's own T cells (a type of white blood cell [WBC]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell culture and animal models of AML and MM. Over the last 5 years we have been preparing to treat patients as part of a Phase I (first in human) clinical trial. The trial treatment involves collecting the patient's own WBCs from the blood by a standard well established and safe process called apheresis. The cells are then cultured in a specialized laboratory (under Good Manufacturing Practice conditions, similar to standards under which pharmaceuticals are produced) over 12 days to convert the cells to specialized tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that is modified so that it cannot infect or replicate outside the special culture conditions) that contains a special gene. Via the virus, this gene inserts into the patient's T cells in culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate, the new gene produces a protein receptor that becomes part of the patient's T cells. This protein receptor on the T cells has the capacity to specifically recognize and bind to a protein on the leukemia or myeloma cells called the "Lewis Y" antigen. After the modified T cells are infused into the patient, they home into the bone marrow (this tracking is monitored by special radiological techniques) where the new protein receptor on the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once bound onto the cancer cells, the T cells get activated and subsequently replicate and kill the cancer cells. The novelty of this approach is that the T-cells will only kill cells that have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side effects. This gene therapy trial is unique and although the primary purpose is to test the safety of this approach, patients will be monitored closely for anti-tumor responses. As the trial progresses, the dose of T cells infused will increase, in the hope that this will result in a better and stronger immune response to the leukemia or myeloma.

Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Since the optimal dosage of this drug has not been found yet, it remains as a subject of clinical study that needs to be examined. If initial toxicity is minimized by developing dosage/regimen that replaces the standard therapy, it will be possible to provide continuous treatment with increased convenience by patients and treating physicians as well as improvement for safety in elderly patients or those with serious cytopenia. In addition, it is expected to lead to a better response by strictly keeping a treatment schedule. Recent US study showed that 5-day regimen showed similar treatment results, but retrospective data from Spain showed lower response rate in 5-day regimen. Considering the recent circumstances around dosage and schedule of azacitidine in lower risk MDS, a Phase II clinical trial is planned in lower risk MDS patients in order to explore the efficacy in 5-day treatment by comparing prospectively with 7-day standard regimen.